Detail TB bacilli under the microscope. | THE WORLD - The Mundo.es

At first glance, tuberculosis disease does not seem problematic. There are treatments that achieve total healing, although 50% of the world’s population is infected with the bacillus that causes the disorder-called Mycobacterium tuberculosis, only between 5 and 10% of those infected develop the disease. However, when looked at a little more closely, you discover quickly that tuberculosis is, in fact, an obstacle difficult to overcome.

In recent years, drug-resistant strains have increased significantly, especially in countries where AIDS is a major scourge, as in Africa, and also in those where crowding and poor treatment strengthens the bacteria , as in Russia. But these are not the only places in which the resistors are strong. In countries like ours, with about 50 cases a year, also show their faces.

The problem with these ‘megabacteria’ is on the one hand, increasing the cost of treatment they need and, second, the possibility that they begin to spread more easily and return to a situation before the ‘age’ of antibiotics.

This situation is intended to prevent research groups throughout the world genome analysis of different strains of ‘M. TB ‘. Although in recent years there have been several studies on the subject, now the journal Nature Genetics just published the largest genome sequencing efforts of the bacillus of tuberculosis.

A mine of information

Made by groups from different countries, among which is Spain , this macro research has been reported by some scientists as a mine of information on how the pathogen has evolved over time and what mutations in its genome allowed him to create resistance against current treatments.

“Until now had approximately 22 sequenced genomes of tuberculosis. Through this work, we have the information of more than 400 strains new . Such studies reflect the fear, the concern that the bacillus fits so well that it becomes the past, with no effective treatment to combat it, “said Charles Martin, researcher Mycobacteria Genetics Group of the CIBER of Respiratory Diseases, who with this group and also from the Department of Microbiology Faculty of Medicine, University of Zaragoza is being devoted to the development of a new vaccine against the disease, which is currently in testing.

Because tuberculosis history is the story of man , as reflected in one of the papers published now and has been led by the Spanish Iñaki Comas, Unit Health and Genomics Research Center Valencia Public Health. After the study of 259 clinical isolates of bacteria (from patient samples) from different geographical areas (Africa, Europe, America, Asia …) and massive genomic sequencing, Comas team was able to determine that the association between TB bacteria and humans is dated to about 70,000 years before humans left Africa.

“We show important parallels between the current geographical distribution of the differences between clinical isolates of bacteria and human populations. This suggests that the bacteria accompanied humans out of Africa and populated the rest of the world, has been able to adapt very small human populations and nomadic tribes in Africa to more sedentary, coinciding with the development of agriculture and livestock, who settled in more or less permanent villages leading to a population explosion and a sharp increase in the population density 10,000 years ago, during the period known as Neolithic “says Comas.

For this reason, says the researcher, one could say that the success of humanity has also led to the success of the bacteria and, consequently, a greater number of cases of illness and deaths. Because in the beginning, the ‘M. tuberculosis’ was less virulent as it was his strategy to avoid extinction, as the only reservoir, the only habitat for this bacterium is human. As the population density was higher and the number of hosts was no problem limiting the pathogen started to become more aggressive .

Keys

against resistance

Throughout this evolution, the bacteria has accumulated at least 30,000 variations in its genome , which are also not many when compared with other pathogens, and may be due to replication is slow “and, because being associated human polymorphism is lost much [DNA changes],” the Valencian researcher.

massive genomic sequencing of this bacillus has not only learn about the changes that have resulted in its history ‘familiar’ but also genomic variations and genes involved with drug resistance. Thus, in the study conducted by Maha Farhat, Massachusetts General Hospital (USA), which sequenced the genome of 123 strains of TB, identified 39 genomic regions associated with resistance . “Some of them have unknown functions, but the rest are associated with the maintenance of the cell wall with enzymes that react to drugs to compensate for their action or directly generate resistance,” he told WORLD Farhat.

In line

was work team David Allan, Infectious Diseases Department at Rutgers University in New Jersey (USA), but focusing on those genetic mutations that confer resistance to one of the drugs of first line in the treatment of tuberculosis, ethambutol . “Our study contradicts the common belief that drug resistance is caused by mutations in a single step. What we have seen, at least with ethambutol, is that the process is complex,” say the researchers in the article.

But what could have clinical relevance of these data? “We hope that these mutations can be used to extend the currently used diagnostic tools,” says Farhat. With new molecular techniques such as those used in these works, you get a much faster and with less risk of biohazard. “We also hope that these mutations may extend our understanding of how they develop drug resistance paving the way for better ways to treat resistant tuberculosis and even achieve the prevention of drug “, indicates this specialist.

aspiration necessary since, according to previous studies, the prevalence of multidrug-resistant and extremely durable reaches or exceeds 10% in some places . When a case appears to treat options are limited, expensive and difficult: the necessary drugs can cost up to 200 times more than those used for common TB. Furthermore, the duration of treatment should be two years, compared to six months in the simplest cases, and side effects can be serious as deafness or psychosis.

Situation in Spain

Sofia Samper, Aragon Institute of Health Sciences (Zaragoza) and CIBERES member, is leading the National database and MDR-TB Iberoamericana that identifies the number of such strains circulating in Spain since which was created in 1998, together with the Institute of Health Carlos III. “There are over 500 registered. We average about 50 cases a year, but we have found that, in recent years, no less, probably coinciding with the departure of immigrants from the country,” he says.

The idea, or the urge to create this record came prompted by the outbreak that occurred in our country in the 90s extremely resistant strain . “Since then, in addition to the database, hospitals were created in separate rooms with a special ventilation system, so that the patient remain isolated there until their disease is no longer contagious, which are available in one or two weeks from the start of treatment in cases of sensitive strains, because if they are multiresistant attention requiring up to two months. “

These improvements in the treatment and monitoring have led in recent years and after stabilization of the HIV epidemic in Spain, TB cases have stabilized and follow the gradual trend to decrease.

“We now have about 15 episodes per 100,000 inhabitants. A third or more are given in immigrants coming to their country already infected or strain have acquired here. But we are fortunate that there are many groups working very well, both from the standpoint of basic and applied. There are powerful groups who are researching a vaccine and also in epidemiology. think that effort has freed us to be having more trouble “says Emilio Bouza, chief of Clinical Microbiology and Infectious Diseases of the Hospital Gregorio Marañón in Madrid.

matches their view Juan Ruiz Manzano, head of the Service of Pneumology, Hospital Germans Trias i Pujol in Badalona, ??who emphasizes that our country is producing a “slow and progressive decrease in the number of cases and a concentration of those in large cities “, as in most developed countries.

This specialist

, despite progress, it is essential to remain vigilant, especially with resistant tuberculosis. “Overall resistances are always the product of human hands. Was produced by a poorly displayed or treatment for premature withdrawal of the medication by the patient. And we must be vigilant to prevent this possibility,” he concludes.

Seeking vaccine

Each year, more than nine million new cases of tuberculosis worldwide and approximately two million people die because of this disease, according to the World Health Organization. Although there are effective treatments against bacillus liable required duration of such therapy, six months at best, and the emergence of resistance to two or more drugs which is leading to increasingly more patients infected for these strains. This is the inability to conduct a treatment in some parts of the world, as it must last for two years and its cost is impossible for both the patient and the health systems of developing countries. Hence, many groups are focused on the search for a more effective vaccine against tuberculosis.

One of them is led by Carlos Martin who, although not the only one involved in that fight does provide a different approach. Other research teams are focused on improving the current inefficient BCG (Bacille Calmette-Guerin), a strain obtained from a tubercle bacillus isolated from cows, and treated to reduce its pathogenicity for humans. “Our vaccine is based on a human strain, which have more than 100 different genes to the BCG. Is a highly attenuated strain which is adapted to both the human body does not produce a disease, but it is visible to the system immune. The aim is that this vaccine train this system of defenses, so be alert and protect against human strains. “

last October authorized the first trial with this vaccine, to test its safety and immunogenicity in 36 healthy adult volunteers at the Hospital of the University of Vaudois (Lausanne, Switzerland). “We expect the first results will be up in October next year and expected immunogenicity data,” says this expert. Of achieved positive results, it would be the first vaccine against TB with a attenuated human strain, developed by a Spanish company Biofabri, with financial support from the Bill & Melinda Gates Foundation and the European Initiative Against Tuberculosis ( TBVI). However, as explained by the ‘father’ of the vaccine, it is a European project that wants to “see if this product is so good in humans as seen in animals”.