Best Treatment For TB Patients, Tuberculosis patients may receive treatments in the future according to what version they have of a single 'Goldilocks' gene.
Tuberculosis - is a common, and in plenty of cases deadly, infectious illness caused by various strains of mycobacteria, usually Mycobacterium tuberculosis.Tuberculosis usually assaults the lungs but can also affect other parts of the body. It is spread through the air when individuals who have an active MTB infection cough, sneeze, or otherwise transmit their saliva through the air.Most infections in humans lead to an asymptomatic, latent infection, and about in0 latent infections finally progress to active illness, which, if left untreated, kills over 50% of those infected.
This is of the first examples in infectious disease of where an individual's genetic profile can select which drug will work best for them - the idea of personalised medicine that is gradually becoming familiar in cancer medicine.
The scientists found that people generate an immune response to tuberculosis that is 'too much', 'too little' or 'just right', according to what versions they have of the LTA4H gene.
Furthermore, the researchers show that steroids used as part of the standard treatment for the most extreme type of tuberculosis, TB meningitis, only benefit some patients.
The results of the study, part-funded by the Wellcome Trust, are published in the journal Cell.
Tuberculosis is a major cause of death worldwide, with an estimated 9.4 million cases and one.7 million deaths in 2009. The disease is caused by Mycobacterium tuberculosis bacteria and differs according to where the infection takes hold. Most TB affects the lungs, but around 40% of cases involve disease elsewhere. In perhaps 1% of cases, TB affects the brain. This type of the disease, TB meningitis, is the most serious. It is hard to diagnose and treat, and even with treatment it is often deadly.
The standard treatment for TB meningitis involves a range of antibiotics to try and kill the bacteria, and the steroid dexamethasone to dampen inflammation - the body's response to tuberculosis infection that can be as much of a controversy.
The scientists identified a gene in zebrafish associated with susceptibility to tuberculosis, which controlled the balance of the inflammatory response. Variations in the DNA code in this gene could fine-tune different biological pathways, leading either to much inflammation or small. Both much and small inflammation were issues, allowing the tuberculosis bacteria to prosper and multiply.
The new study combines work in zebrafish at the University of Washington, Seattle to identify genes and biological pathways involved in the immune response to TB, with clinical research work in collaboration with Pham Ngoc Thach Hospital, the Hospital for Tropical Diseases and the Oxford University Clinical Research Unit in Vietnam.
The researchers showed that blocking the appropriate biological pathway with drugs could restore the right level of inflammatory response.
The researchers based in Vietnam then returned to samples from a earlier clinical trial in over 500 patients with TB meningitis. They showed changes at a single position in the human LTA4H gene were associated with treatment response.
Only those having LTA4H genes that led to much inflammation benefitted from the use of the steroid dexamethasone.
There is some suggestion that the steroid could have an adverse effect for those whose LTA4H genes already lead them to have a reduced inflammatory response, though the result is not statistically significant.
This study highlights the power of really good clinical research supported through Wellcome Trust Fellowships and linked with some of the very best scientists in the world in Vietnam and the USA, which can bring immediate benefits to patients and also point the way to develop better, more targeted drugs to treat people with tuberculosis in the future.
