Mutant gene linked to most severe type of TB

People who carry a mutant gene can develop potentially fatal meningitis if they get infected with the drug resistant Beijing strain of tuberculosis, a study in Vietnam has found.

Tuberculous meningitis is the most severe form of the disease in which the infection spreads to membranes enveloping the brain and the spinal cord. One in three people who develop TB meningitis dies, even if he or she gets hospital treatment.

The study published in the open-access journal PLoS Pathogens (plospathogens.org), found people most likely to develop TB meningitis were those who carried a variant of the TLR2 gene and who get infected with the Beijing TB strain, prevalent in Asia and the former Soviet states.

Previous studies have linked TLR2 to the immune system and it seems to be important for recognising and initiating a defensive response to the TB bacteria.

The researchers took bacteria samples from 187 patients who suffered tuberculous meningitis and 236 other patients who suffered the more common pulmonary tuberculosis.

Most of the patients then had their genes analysed to see if they carried the TLR2 variant.

"Together, these results suggest that the association of the (variant gene) with tuberculous meningitis is strongest among those infected with the Beijing lineage," the scientists wrote.

The "Beijing" family of TB strains is prevalent in Asia and former Soviet states. It has become more drug resistant in recent years and has been responsible for outbreaks of multi-drug resistant tuberculosis in the United States.

More than one-third of the world's population is infected with TB and the infection rate is one every second. However, only one in 10 infected persons will develop symptoms and that usually happens when their immune systems are weak.

Left untreated, TB kills half its victims. The disease kills over 2 million people each year.

One of the researchers, Maxine Caws at the Hospital for Tropical Diseases in Vietnam, said the latest finding was a reason to develop more sophisticated and targeted treatments and vaccines.

"This is particularly important in this era of emerging 'untreatable' bacteria infections due to antibiotic resistance," Caws wrote.

Under-the-tongue vaccine may be best to lick flu

Administering flu vaccines under the tongue may be more effective and offer more protection than injecting or inhaling the drug, a study with mice in South Korea has found.

"It (the base of the mouth) is a very good absorbent and competent tissue ... in taking vaccine and presenting it to the immune system ... to initiate an immune response," Cecil Czerkinsky, biological sciences professor at the Seoul National University, said in a telephone interview.

There is currently no vaccine that is administered under the tongue, or what is known as the sublingual area.

But there have been recent studies testing its effectiveness in inducing immune responses in mucosal tissues in the respiratory system, gut and inside of the cheek, and blood.

In an article published in the Proceedings of the National Academy of Sciences, the researchers described how they administered both live and killed flu vaccines under the tongues of mice and then exposed the rodents a few weeks later to lethal doses of influenza viruses.

"All the mice were protected ... they (vaccines) also gave cross-protection to other flu viruses," Czerkinsky said.

Unlike injected vaccines, which induce antibody production mainly in the blood, the sublingual method "induced antibodies in both lungs (mucosal lining) and the blood," he said.

"Influenza is a mucosal disease. That (sublingual method) is better because then you tackle the infection at the very early stage before the infection (goes to the blood)."

Such a method is different from the oral route, often seen as subjecting drugs to the erosive effects of digestive fluids.

The correct way to do it would be for the person to hold the vaccine in the base of the mouth for about 30 seconds.

"In 30 seconds, the sublingual area absorbs the vaccine and immediately the vaccine is taken up and processed by the immune system and it initiates very rapid stimulation of antibodies, within days," Czerkinsky said.

The study also suggested that this method may be safer than administering vaccines intranasally, or through inhaling.

There are nerve fibres in the nose, which opens up the possibility, however rare, that viruses in vaccines could enter the central nervous system, the researchers said.

Control groups of mice were given vaccines intranasally. The scientists later detected virus in the olfactory nerves of mice that were given vaccines containing killed viruses, which raised safety questions.

Mice that were given vaccines containing live, attenuated virus intranasally all died very quickly.

The scientists plan to conduct a clinical study later this year.