Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin

在过去十年中，5岁以下儿童的死亡率显著降低。然而，这种减少主要发生在1个月以上的儿童；在新生儿（从出生到一个月大）中没有观察到变化。这一年龄组的死亡率占5岁以下儿童死亡总数的一半。在新生儿死亡率最高的20个国家中，有16个位于撒哈拉以南非洲。1990年，联合国制定了千年发展目标（mdgs），旨在到2015年改善最贫困人口的生活条件。千年发展目标4旨在将五岁以下儿童死亡率降低三分之二，这一目标只有在新生儿死亡率大幅降低的情况下才能实现。严重细菌性疾病是新生儿死亡的主要原因之一。在撒哈拉以南非洲，不同的细菌在生命的第一个月内导致这些死亡。严重的新生儿疾病发生在细菌感染之后。个体感染后可不发病（携带期），但随后发病需要感染。在撒哈拉以南非洲，细菌携带（即在产道和/或鼻咽道）非常普遍，其结果是细菌性疾病的发病率是世界上最高的之一。新生儿可在分娩期间（通过产道时）感染，也可在出生后的头几天/几周内感染，因为与母亲有密切的身体接触，如果母亲在鼻咽道中携带细菌。如果母亲是新生儿细菌感染的重要来源，在分娩期间对母亲进行强效抗生素治疗应可减少细菌携带，从而减少新生儿在出生后最初几天/几周内被细菌传染的风险，从而降低严重细菌性疾病的发生率，从而降低死亡率。在提出的研究中，我们将确定在分娩期间给予母亲单一剂量的抗生素是否会减少新生儿在生命的第一个月内的细菌携带。我们选择了一种抗生素（阿奇霉素），这种抗生素在撒哈拉以南非洲已经显示出对细菌鼻咽携带和社区中所有人服用（大规模给药）时的全因死亡率有很强的影响。这种特殊的抗生素在非洲农村作为一种简单的干预措施部署有几个优点，即它需要一次口服给药，没有特殊的储存要求，并且有可能消除大多数通常导致新生儿严重疾病的细菌。将在西冈比亚的一个农村卫生机构进行一项临床试验，以评估在分娩期间对新生儿在生命最初几周内的细菌感染进行治疗的效果。如果显示出影响，下一步将是进行一项更大规模的研究，旨在确定在较低护理水平下实施的干预措施（因为大多数非洲妇女在传统助产员的协助下在家分娩）是否减少了新生儿侵袭性细菌疾病的发生。

The last decade has witnessed an important reduction of the mortality in children less than 5 years of age. Nevertheless, such reduction occurred mainly in children older than 1 month; no change was observed in newborns (between birth and one month of age). Mortality in this age group contributes half of all deaths occurring in children below 5 years of age. Sixteen out of the 20 countries with the highest neonatal mortality are in sub-Saharan Africa. In 1990, the United Nations established the Millennium Development Goals (MDG) aiming at improving by 2015 living conditions of the poorest populations. The MDG number 4 aims at reducing by two-thirds the under-five mortality, a result attainable only with a substantial reduction in neonatal deaths.Severe bacterial disease is among the leading causes of neonatal deaths. In Sub-Saharan Africa, different bacteria are responsible for these deaths during the first month of life. Severe neonatal disease follows bacterial infection. Individuals can be infected without developing disease (carriage stage) but infection is needed to subsequently develop disease. In Sub-Saharan Africa, bacterial carriage (i.e. in the birth canal and/or nasopharyngeal tract) is very common, with the consequence that the occurrence of bacterial disease is one of the highest in the world. Newborns can be infected during labour - when passing through the birth canal - and also during the first days/weeks of life, as a consequence of the close physical contact with the mother, if the latter carries bacteria in the nasopharyngeal tract. If the mother is an important source of bacterial infection to the newborn, treating mothers with a powerful antibiotic during labour should decrease bacterial carriage and therefore diminish the risk of bacterial transmission to the newborn during the first days/weeks of life, which should in turn result in the lower occurrence of severe bacterial disease and hence lower mortality. In the study proposed, we will determine whether a single antibiotic dose given to the mother during labour decreases the bacterial carriage of the newborn during the first month of life.We have selected an antibiotic (azithromycin) that in Sub-Saharan Africa has already shown both a strong impact on bacterial nasopharyngeal carriage and on all-cause mortality when administered to everybody in a community (mass drug administration). This specific antibiotic has several advantages for being deployable as a simple intervention in rural Africa, i.e. it requires a single oral administration, it has no special storage requirements and it has the potential to eliminate most of the bacteria commonly causing severe disease in newborn. A clinical trial will be conducted in a rural health facility in Western Gambia to evaluate the effect of treating mothers during labour on bacterial infection in the newborn during the first weeks of life. If an impact is shown, the next step would be to conduct a larger study aiming at establishing if the intervention, implemented at a lower level of care (as most African women deliver at home assisted by traditional birth assistants), decreases the occurrence of neonatal invasive bacterial disease.