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

产前给予阿奇霉素预防新生儿细菌感染

• 批准号: MC_EX_MR/J010391/1
• 负责人: Anna Roca
• 金额: $ 71.31万
• 依托单位: MRC Unit the Gambia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_MR%2FJ010391%2F1
• 关键词: Prevention; bacterial; infections; newborn; pre

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.

在过去十年中，5岁以下儿童的死亡率大幅下降。然而，这种减少主要发生在1个月以上的儿童中;新生儿（出生至1个月大）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。新生儿死亡率最高的20个国家中有16个在撒哈拉以南非洲。1990年，联合国制定了千年发展目标，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，这一结果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，不同的细菌是造成这些死亡的第一个月的生活。严重的新生儿疾病是由细菌感染引起的。个体可以在没有发展疾病的情况下被感染（携带阶段），但需要感染才能随后发展疾病。在撒哈拉以南非洲，细菌携带（即在产道和/或鼻咽道中）非常常见，其结果是细菌性疾病的发生率是世界上最高的之一。新生儿可能在分娩过程中-通过产道时-以及在出生后的最初几天/几周内受到感染，这是由于与母亲的密切身体接触，如果后者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，则在分娩期间使用强效抗生素治疗母亲应减少细菌携带，从而降低新生儿在生命的最初几天/几周内细菌传播的风险，这反过来又会降低严重细菌性疾病的发生率，从而降低死亡率。在这项研究中，我们将确定在分娩过程中给予母亲单一剂量的抗生素是否会减少新生儿在出生后第一个月的细菌携带。我们选择了一种抗生素（阿奇霉素），在撒哈拉以南非洲，当给社区中的每个人服用时，它已经显示出对细菌鼻咽携带和全因死亡率的强烈影响（大规模药物管理）。这种特定的抗生素具有几个优点，可以在非洲农村作为简单的干预措施部署，即它需要单次口服，它没有特殊的储存要求，并且它有可能消除大多数通常导致新生儿严重疾病的细菌。将在冈比亚西部的一个农村保健设施进行一项临床试验，以评价在分娩期间治疗母亲对新生儿出生后最初几周内细菌感染的影响。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上实施的干预措施（因为大多数非洲妇女在传统助产士的帮助下在家中分娩）是否减少了新生儿侵入性细菌疾病的发生。

项目成果

Impact of Intrapartum Oral Azithromycin on the Acquired Macrolide Resistome of Infants' Nasopharynx: A Randomized Controlled Trial.

• DOI: 10.1093/cid/ciaa609
• 发表时间: 2020-12-15
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Bojang A;Baines SL;Camara B;Guerillot R;Donovan L;Marqués RS;Secka O;D'Alessandro U;Bottomley C;Howden BP;Roca A
• 通讯作者: Roca A

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis.

• DOI: 10.1136/thoraxjnl-2016-209421
• 发表时间: 2017-06
• 期刊: Thorax
• 影响因子: 10
• 作者: Dodd PJ;Prendergast AJ;Beecroft C;Kampmann B;Seddon JA
• 通讯作者: Seddon JA

Why the Convention on the Rights of the Child must become a guiding framework for the realization of the rights of children affected by tuberculosis.

• DOI: 10.1186/s12914-016-0105-z
• 发表时间: 2016-12-08
• 期刊: BMC international health and human rights
• 影响因子: 3
• 作者: Basu Roy R;Brandt N;Moodie N;Motlagh M;Rasanathan K;Seddon JA;Detjen AK;Kampmann B
• 通讯作者: Kampmann B

Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

• DOI: 10.1093/cid/ciy254
• 发表时间: 2018-09-28
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Bojang A;Camara B;Jagne Cox I;Oluwalana C;Lette K;Usuf E;Bottomley C;Howden BP;D'Alessandro U;Roca A
• 通讯作者: Roca A