According to a study published in the open-access journal PLoS Pathogens, researchers working in Vietnam have found that people with a particular genetic variant and who are infected with a strain of tuberculosis (TB) known as the Beijing strain are predisposed to developing a lethal form of TB called tuberculosis meningitis. Sarah Dunstan (Wellcome Trust Major Overseas Programme, Hospital for Tropical Diseases, Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam) and colleagues maintain that the study highlights why it is important to study both sides of the host-pathogen interaction.
TB is caused by the bacterium Mycobacterium tuberculosis and results in over 2 million deaths every year. Researchers presume that although the majority will never present symptoms, over 2 million people are infected with M. tuberculosis. For some people, symptoms of a latent infection will only show if they become sick or become infected with a disease that attacks the immune system, such as HIV. Few will develop a TB infection in the lungs that will spread to the rest of the body (called “disseminated TB.”) This happens when the immune system fails to control the infection.
HIV infection, malnutrition, and smoking are risk factors that increase the likelihood of developing active TB after exposure. In previous research, Dunstan and colleagues found a link between the gene TLR2 and TB susceptibility. TLR2 is a gene involved in the immune system that is crucial for recognizing when a bacterium enters the body and then initiating an immune response.
It is common for people in the Vietnamese population to have a particular variant of TLR2 that increases their likelihood of developing the most severe form of TB – when the disease infects the membranes that envelope the brain and the spinal cord, called meninges. Even if sufferers are treated in hospitals, the death rate for TB meningitis is about 33%.
The researchers in Vietnam have shown that there is a strong predisposition to developing TB meningitis for people who have the TLR2 gene variant and who have the Beijing TB strain.
Co-author Maxine Caws says that, “We are seeing an increasing number of cases of the Beijing strain worldwide, a strain that is becoming more and more resistant to drugs.” According to The World Health Organization, about 5% of world TB cases resistant to multiple drugs. Without effective treatments, the mortality rate approaches 100% in people with types of strains like TB meningitis.
“Our findings are important because they show that we need to look at both the patient’s susceptibility to the disease and the genetics of the pathogen that is infecting them at the same time,” notes Dr Caws. “Many studies have shown a genetic association with disease in one population but the finding has not been repeated in different populations. This might be not only because of ethnic differences in the population, but also because the pathogen populations are different.”
The researchers conclude: “Understanding the mechanisms that influence our susceptibility to infectious diseases may allow us to develop more sophisticated and targeted treatments and vaccines. This is particularly important in this era of emerging ‘untreatable’ bacterial infections due to antibiotic resistance.”
The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis
Caws M, Thwaites G, Dunstan S, Hawn TR, Lan NTN, et al.
PLoS Pathogens (2008). 4(3):e1000034.
doi:10.1371/journal.ppat.1000034
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Written by: Peter M Crosta