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- An easy task: scientists have assessed the risk of spreading a mutant strain of tuberculosis
An easy task: scientists have assessed the risk of spreading a mutant strain of tuberculosis
The genotype of antibiotic-resistant tuberculosis bacteria SIT266 may be widespread in our country, Russian scientists believe. This includes the EurA1.1 mutant strain, which was previously identified in Karelia, Pskov and Novgorod regions. Due to the drug resistance of this type of pathogen, an individual treatment regimen must be selected for people infected with it. And because of the genetic similarity, during diagnosis, it can be confused with a close, but much less dangerous "relative." However, this option does not cause particularly severe symptoms or rapid development of the disease. The main thing is to identify its carriers in time so that the infection does not become widespread.
The spread of a dangerous mutant strain of tuberculosis
The genotype of antibiotic-resistant tuberculosis SIT266, which includes the EurA1.1 strain, previously identified in several regions of Russia, may spread widely across the country, according to Russian scientists. At the same time, it is unlikely to cause an epidemic, they noted.
""There is a risk of widespread spread, especially if the disease is detected late or the treatment is incorrect, but there is no reason to talk about an imminent mass epidemic," Albert Rizvanov, head of the Center for Excellence "Personalized Medicine" at Kazan Federal University, told Izvestia.
The genotype of tuberculosis bacteria SIT266 is dangerous primarily due to its resistance to several anti-tuberculosis drugs at once. However, there is no evidence that it itself is more contagious than ordinary tuberculosis. But it can be transmitted from person to person in a stable form, and this makes it a problem for public health. It can be treated, but first you need to determine which drugs a particular bacterium is still sensitive to, and then choose a combination of several active drugs.
A recent study by European researchers has shown that the EurA1.1 mutant strain, which belongs to the SIT266 genotype, is actively circulating in Russia. The fact that the strain is found in Russia was also confirmed by the National Research Medical Center of Phthisiopulmonology and Infectious Diseases of the Russian Ministry of Health.
According to the relevant institute, it was first discovered in Belarus. In addition to the main focus in this country, the treasure was also identified in the north-west of Russia — in the Pskov, Novgorod regions and Karelia. According to Anna Panova, head of the scientific Department of Microbiology and Molecular Genetics at the center, it is now "not dominant among other mycobacterium genovariants."
But the chances of a massive spread of the mutant strain are high, says molecular biologist Arina Kholkina.
— In Belarus, it has caused a large number of cases of resistant tuberculosis, and traces of it are already being found in Russia and Europe. This indicates a cross—border spread, and the chances of its further spread in the population are estimated to be high, which requires close epidemiological surveillance," the expert said.
It is impossible to defeat the strain using conventional schemes — an individual selection of drugs is needed based on a complete "reading" of the bacterial genome. It's like choosing a key to a unique lock, rather than acting at random, Arina Kholkina explained.
Russian doctors have everything they need to combat different strains of tuberculosis, Vadim Testov, First deputy director of the National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Russian Ministry of Health, told "Izvestia". According to him, the EurA1 strain corresponds to the previously described SIT266 spolygotype.
— Current Russian clinical guidelines include all current chemotherapy regimens with a high level of evidence, and technologies for rapid determination of resistance have been implemented in all regions of the country. It is important that today we are independent of imports: all medicines and rapid diagnostic test systems are manufactured by Russian companies. In particular, scientists at the National Research Medical Center of the Russian Ministry of Health have developed an automated device for rapid determination of drug resistance at the patient's bedside," said the doctor.
Treatment of a resistant strain
In 2013, the staff of the Republican Scientific and Practical Center of Pulmonology and Phthisiology in Minsk examined more than 80 samples of tuberculosis bacteria, 30% of which belonged to SIT266. All of them were insensitive to the drugs rifampicin, isoniazid, streptomycin and ethambutol.
The scientists compared their genomes and found out that the representatives of this group had the same specific mutation (Asp94Gly) in the pncA gene responsible for pyrazinamide resistance. At the same time, it was not possible to identify the common source of infection among those infected, which, according to scientists, indicates the prevalence of the variant. For the treatment of tuberculosis caused by it, a special scheme is required.
— For such isolates, it is fundamentally important to individually determine drug sensitivity to drugs used in drug-resistant tuberculosis treatment regimens. With continued sensitivity to bedaquiline and linezolid, modern fully oral regimens are possible," said Anna Panova, Head of the Scientific Department of Microbiology and Molecular Genetics at the National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Russian Ministry of Health.
According to Andrey Pozdnyakov, an infectious disease specialist at "Invitro", SIT266 is difficult to treat.
— The main problem is that it is resistant to most of the "old" drugs and is rapidly developing resistance to new ones used in alternative treatment lines, such as linezolid and fluoroquinolone. However, it does not often cause severe forms," the doctor said.
In 2016, researchers at the Pasteur Research Institute analyzed two SIT266 samples collected in 2014, which they call an epidemiologically significant genotype. They identified mutations in him that cause drug resistance. However, due to its genetic similarity, it is very often confused with the related but much less dangerous SIT264.
— With a similar but less dangerous strain of SIT264, he behaves like an impostor double. There is an insert in its DNA that masks one section, and a routine test confuses a dangerous strain with a safe one. Therefore, they can only be reliably distinguished using complete genome sequencing and bioinformatic analysis," said Arina Kholkina.
For the usual diagnosis of tuberculosis, this similarity does not pose a big problem: the laboratory will determine the presence of the infection itself. The difficulty arises at the next stage, when scientists are trying to determine exactly which genetic variant the bacteria belong to, Albert Rizvanov said.
— SIT266 can indeed be mistaken for SIT264 due to the peculiarities of one region of the genome. This is important primarily for epidemiologists: if such errors occur frequently, the actual spread of SIT266 may be underestimated. Modern genome—wide sequencing and a separate search for drug resistance mutations can significantly reduce this problem," he said.
Modern sequencing methods make it possible to accurately distinguish even similar variants of mycobacteria, noted Andrey Pozdnyakov. Confusion is possible only if outdated equipment is used in diagnostics.
— This mutation of Mycobacterium has been known recently and requires close study. But first of all, we need to control its distribution. Such patients with open forms should be isolated and treated in phthisiological departments so as not to spread this type of mycobacteria to the masses," the doctor said.
They need to be diagnosed with the most modern diagnostic methods in order to identify multidrug-resistant strains and select those drugs to which this pathogen is sensitive. At the same time, it is important to monitor the possible side effects of their various combinations, the infectious disease specialist emphasized.
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