The impact of maternal infection with Mycobacterium tuberculosis on the infant response to BCG immunisation

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Tuberculosis (TB) is still a very important health problem in sub-Saharan Africa. Many people are infected with Mycobacterium tuberculosis (M.tb) (the bacterium that causes tuberculosis) in these countries, but the infection is kept in check by the immune system and the people remain healthy. We call this latent infection. Usually, only about 10% of infected individuals will progress to having the active form of the disease in their lifetime. However, when people do get the active disease, they can infect many other people, and so the cycle continues. TB kills approximately 2 million people every year, and another 10 million people become infected with M.tb every year. One way to eradicate TB would be to immunise everyone with an effective vaccine. Unfortunately, to date there is only one licensed vaccine, BCG, which was first introduced almost 100 years ago. BCG is given in many countries at, or around the time of birth. In sub-Saharan Africa, this immunisation schedule has been very effective at preventing some of the more severe (and deadly) forms of the disease in children, but the vaccine does not protect against the more common, active pulmonary form of the disease (the disease affecting the lungs) that occurs in adolescents and adults. By contrast, in countries such as the UK, BCG immunisation gives up to 80% protection against active pulmonary disease in adolescents and adults. We do not know why BCG should give poorer protection against pulmonary TB in sub-Saharan African countries compared to European countries, and our study is aimed at understanding this phenomenon.Since latent M.tb infection is more prevalent in sub-Saharan Africa than in the UK (for example), we think that part of the answer may lie in whether a mother has an underlying, latent M.tb infection. We think that this infection in a pregnant woman may affect the developing baby's own immune system. For example, if the baby is exposed to maternal M.tb infection while in the womb, when its immune system is developing, the immune system may regard the presence of Mtb infection as "normal" and fail to mount a suitable reaction to the infection. In such a case, when the baby is born and is given the BCG vaccine, the baby may not respond in the same way as a baby who was born of a mother without a latent M.tb infection (such as mothers in the UK).Our study will therefore look at the infant immune response to the BCG vaccine. We will examine immune responses in babies born in sub-Saharan Africa from mothers who do and don't have a latent M.tb infection, and we will compare their results with results from babies born of mothers in the UK, where M.tb infection is much less common. These results will give us a good idea of whether maternal M.tb infection status affects the infant response to BCG. If it does, then we may have to think about testing young women for the infection, and treating them before or during pregnancy.