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

结核病在撒哈拉以南非洲仍然是一个非常重要的卫生问题。在这些国家，许多人感染了结核分枝杆菌（M.tb）（引起结核病的细菌），但这种感染受到免疫系统的控制，人们保持健康。我们称之为潜伏感染。通常，只有约10%的感染者会在其一生中发展为活动性疾病。然而，当人们患上活动性疾病时，他们可以感染许多其他人，这样循环就会继续下去。每年约有200万人死于结核病，另有1000万人感染结核分枝杆菌。根除结核病的一种方法是给每个人接种有效的疫苗。不幸的是，迄今为止只有一种获得许可的疫苗，即卡介苗，它是在近100年前首次引入的。许多国家在婴儿出生时或前后接种卡介苗。在撒哈拉以南非洲，这种免疫接种计划在预防儿童中某些更严重（和致命）的疾病方面非常有效，但疫苗不能预防发生在青少年和成人中更常见的活动性肺部疾病（影响肺部的疾病）。相比之下，在英国等国家，卡介苗免疫对青少年和成人活动性肺病的保护作用高达80%。我们不知道为什么在撒哈拉以南非洲国家，与欧洲国家相比，卡介苗对肺结核的保护较差，我们的研究旨在理解这一现象。由于潜伏性结核分枝杆菌感染在撒哈拉以南非洲比在英国更为普遍（例如），我们认为部分答案可能在于母亲是否有潜在的潜伏性结核分枝杆菌感染。我们认为孕妇的这种感染可能会影响发育中的婴儿自身的免疫系统。例如，如果婴儿在子宫内暴露于母体结核分枝杆菌感染，当其免疫系统正在发育时，免疫系统可能将结核分枝杆菌感染的存在视为“正常”，而不能对感染产生适当的反应。在这种情况下，当婴儿出生并接种卡介苗时，婴儿的反应可能与没有潜伏结核分枝杆菌感染的母亲（如英国的母亲）所生的婴儿不同。因此，我们的研究将着眼于婴儿对卡介苗的免疫反应。我们将检查撒哈拉以南非洲母亲是否有潜伏性结核分枝杆菌感染所生婴儿的免疫反应，并将其结果与英国母亲所生婴儿的结果进行比较，在英国，结核分枝杆菌感染要少见得多。这些结果将使我们更好地了解母体结核分枝杆菌感染状况是否会影响婴儿对卡介苗的反应。如果确实如此，那么我们可能不得不考虑对年轻女性进行感染检测，并在怀孕前或怀孕期间对她们进行治疗。

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.