Refusing to accept the death toll from drug-resistant TB

Epidemiological studies estimate that nearly nine million people were suffering from active tuberculosis (TB) in 2010, causing upwards of one and a half million deaths. More than 90% of these deaths took place in low- or middle-income countries, thus reinforcing an old idea that TB and poverty are strongly linked. Scientific and technological progress, though, are on the verge of offering new weapons in the fight against TB. Will they be enough to break through the barriers currently facing clinicians and public health officials?

Vaccinations have curbed certain severe forms of the disease among children, but the vaccine - developed in the 1920s - has never stopped inter-human transmission. The main diagnostic test in use since the late 19th century is so poorly sensitive that it identifies fewer than half of active cases. The discovery of streptomycin in 1943 and the organization of one of the first clinical trials in the history of medicine in 1948 comparing it against the benchmark surgical treatment of collapse therapy were both decisive advances. It is nevertheless important to note that the decline of TB in Europe preceded the development of effective therapies, and according to most historians resulted from improved living conditions rather than medical interventions.

The appearance of the new antibiotic rifampicin at the end of the 1950s meant that treatment could be reduced from one year to six months. During the 1990s, increased use of rifampicin and the introduction of the DOTS approach allowed national programs to increase the number of patients cured. The new protocols revived hope that transmission could be disrupted by medical treatment, causing the disease to eventually disappear. The 1980s and 1990s, however, also saw the emergence of the HIV/AIDS epidemic. HIV indirectly aggravated tuberculosis rates by creating a favorable environment for opportunistic infections, among which TB most often causes death. Joint treatment of the two infections has therefore been emphasized over the last few years. But we should not forget that 85% of people suffering from TB do not have HIV/AIDS, demonstrating the need for a concentrated effort to treat TB separately from its treatment as an opportunistic infection linked to HIV/AIDS.

The limits and failures of the medical approach have long been played down by transnational institutions like the International Union Against Tuberculosis and Lung Disease, Stop TB Partnership, and the World Health Organization (WHO), which seek above all to avoid bad news that might discourage wealthy states from financing the fight against TB. In general, donor organizations don't like financing the treatment of diseases (which is, economically speaking, a bottomless pit), preferring instead funding actions that lead to disease eradication. The historic model that comes to mind is smallpox, but in the absence of an effective vaccine, experts have thought that eradication might be possible through treatment of active pulmonary TB responsible for inter-human transmission.

There is another factor hindering recognition of the gravity of the situation at the national level: the worst-affected countries don't appreciate seeing their names linked to a disease that carries the stigma of poverty. This explains why organizations fighting TB, whether national or transnational like the WHO continue to publish data from national programs that are simply too good to be true. In the same spirit, many experts claim that the existing diagnostic, medical, and vaccination tools are enough to eradicate the disease.

Despite such optimism, it became imperative in the 1990s to launch new research programs in order to upgrade the available medical products used for treating TB. Sixty years after the discovery of streptomycin (the first effective antibiotic treatment for TB), the hopes of seeing TB rates seriously reduced by medical interventions were not being met. A number of problems with the tools employed help explain this failure: an ineffective vaccine, an inaccurate diagnostic test, and an overly long treatment regimen with considerable side effects that was tedious for patients to undergo and complicated for doctors to administer. The failure to control the disease at the population level also created difficulties for controlling the disease at the individual level and cure a doubtlessly limited but nevertheless growing number of cases. Throughout the 1990s, treatment-resistant TB epidemics were recorded in the North, as in New York City in 1991 (198 cases.)

At the same time, treatment-resistant epidemics appeared in Russia and Central Asia, confirming a worsening situation where more than one patient in three presented with resistant TB strains. A 2005 epidemic in South Africa of extremely-resistant forms - practically incurable - confirmed the gravity of the worsening situation. Finally, the emergence of "totally resistant" TB epidemics, as in Bombay in 2012, seemed to offer the final word on our inability to control the disease.

The anxiety provoked by resistant forms of known diseases (malaria, tuberculosis) combined with the emergence of new epidemics (HIV/AIDS, Ebola virus) reignited the battle against infectious diseases. Powerful nations worried about their own health security and wanted to prevent the potentially disastrous cost of certain epidemics. Governments were not blind to the fact that political opponents would take advantage should deaths from infectious diseases get out of control. To avoid the chance that a health crisis might become a political crisis, it was important for leaders to claim that the threat had been identified and a response initiated. At a G8 meeting dedicated to infectious diseases in Okinawa in 2000), member states decided to re-launch the fight against infectious diseases. The Global Fund for Aids, Tuberculosis and Malaria was established in 2002 to increase funding for the response to those diseases, and for TB, three new institutions were created in the form of public-private partnerships: the TB Alliance (2000) for Treatment, Aeras (2003) for vaccines, and Find (2003) for diagnostics.

A decade later, we can scrutinize the initial results from these initiatives. Have they been worth the time and money? The subject merits a detailed study that would not shy away from scrupulous examination of the conflicts of interest between private partners (such as pharmaceutical multinationals) and public service partners (national tuberculosis programs and transnational organizations). If the timeline for a new vaccine seems a little long (at least ten years), improved diagnostics have already been facilitated by the introduction of a new test, GeneXpert®, which represents an unmistakable advance even though it doesn't yet meet the optimal specifications sought by practitioners. New molecules, particularly those from Tibotec and Otsuka labs, are now in the final stage of development. The development of several new antibiotics - the first in fifty years - including bedaquiline promises some relief in the short term. Their arrival means the possibility of shortening treatment from several months to a few weeks; in combination, though, they could also cure forms resistant to currently used antibiotics. Will these advances eventually interrupt TB transmission within the societies where it is most deadly? That remains to be seen. To achieve such a radical goal would require changes to a host of social, cultural, economic, and political parameters that are outside the realm of medical intervention.

Despite the uncertainty that initially accompanies any innovation; urgent action must be taken to help those patients who face a critical situation today. Current treatment for drug-resistant TB lasts two years, is extremely toxic, is extremely expensive, and is successful in only half of the cases. Such patients - an estimated half-million new cases each year - need the benefits of new antibiotics as soon as possible. While scientific progress offers hope, other experiences (especially in the battles against malaria and AIDS) invite prudence. Without social and political mobilization, it is unlikely that a new generation of treatments will be made rapidly accessible to those who need them now to survive. In the early 2000s, supply problems (high prices and doubtful quality), administrative hurdles concerning importation, and the sluggishness of health authorities to adopt new therapeutic recommendations were daily barriers to medical teams who wanted to improve treatments for infectious disease. Today, let us hope that humanitarian doctors can act as quickly as possible in prescribing these new antibiotics because they represent the last hope for patients dying from drug-resistant TB.