A trial of the benefit of including azithromycin in the drug combination used for seasonal malaria chemoprevention in African children

将阿奇霉素纳入非洲儿童季节性疟疾化学预防药物组合中的益处试验

• 批准号: MR/K007319/1
• 负责人: Brian Greenwood
• 金额: $ 544.03万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK007319%2F1
• 关键词: trial; benefit; including; azithromycin; drug

Good progress is being made in controlling malaria in Africa but success has been only partial. In some countries there has been only a modest decline in the incidence of malaria despite the widespread deployment of insecticide treated bed nets , spraying of the inside of houses with insecticide and treatment of clinical cases with highly effective drug combinations based on compounds derived from the plant Artemisia annua . More efforts need to be made to scale up these interventions but additional control tools are needed. One potential new tool is seasonal malaria chemoprevention (SMC). SMC involves the administration of a treatment dose of an effective antimalarial drug combination to all children at risk during a period of maximum risk of infection. This approach to malaria control is targeted specifically at areas where malaria transmission is limited by climatic factors to only a few months of the year so that drugs do not have to be given on more than three or four occasions. Areas where SMC would be an appropriate intervention include most of the Sahel and sub-Sahel (population approximately 200 million). Studies conducted in areas of seasonal malaria transmission have shown that SMC with the combination of sulphadoxine/pyrimethamine (SP) and amodiaquine (AQ) reduced the incidence of severe and uncomplicated malaria by over 70% and probably reduced deaths. The intervention was safe, well tolerated and highly cost effective. Anti-malaria drugs were given successfully and safely by village volunteers. A WHO Policy Advisory Committee has recently reviewed the results of trials of SMC and is likely to recommend this as a malaria control intervention for areas with highly seasonal malaria transmission.Despite the success of SMC with SP and AQ in reducing malaria, children in the trials of this intervention still suffered many episodes of infectious diseases, some severe and some fatal. It is likely that the majority of these severe illnesses were caused by bacterial infections. Thus, it is possible that adding an antibiotic to the treatment regimen used for SMC could provide added benefit by preventing severe bacterial infections and hence reducing severe illnesses and perhaps deaths. The most suitable antibiotic to be used in this way is azithromycin (AZ). AZ has been given as mass treatment to millions of healthy children to control trachoma (a bacterial eye infection that can lead to blindness) and shown to be safe and well tolerated. Surprisingly, when AZ was deployed in a trachoma elimination programme in Ethiopia, overall child mortality fell by approximately 65%. If AZ really does prevent deaths in young children, it is likely that it does so by preventing bacterial infections, particularly those caused by the pneumococcus, an important cause of death and severe illnesses in young African children. Thus, it is biologically plausible that adding AZ to SMC regimens might provide additional benefit. To test this hypothesis, a trial will be conducted in approximately 16,000 children in areas of Burkina Faso and Mali where malaria transmission is highly. Children will be randomly allocated to receive SMC with SP+AQ either with or without the addition of AZ. Children will be followed carefully throughout the 2013 malaria transmission season (July-October). All deaths or hospital admissions will be recorded and clinic attendances with a febrile illness will be noted. At the end of the transmission season, a random sample of 4,000 children will be examined and tested for malaria and anaemia. Malaria parasites will be tested at this time for their sensitivity to SP and pneumococci, obtained from the nose, for their sensitivity to AZ. The costs of adding AZ to the SMC regimen and its acceptability will be determined.The results of this trial should establish clearly whether adding AZ to the regimen of SP+AQ used for SMC provides added benefit and, if it does, whether this is safe and cost effective.

非洲在控制疟疾方面取得了良好进展，但只是部分成功。在一些国家，尽管广泛使用经过杀虫剂处理的蚊帐、在房屋内部喷洒杀虫剂以及使用基于植物化合物的高效药物组合来治疗临床病例，但疟疾发病率仅略有下降。黄花蒿。需要付出更多努力来扩大这些干预措施，但也需要额外的控制工具。一种潜在的新工具是季节性疟疾化学预防（SMC）。 SMC 涉及在感染风险最大期间向所有处于危险中的儿童施用治疗剂量的有效抗疟药物组合。这种疟疾控制方法专门针对那些受气候因素影响，疟疾传播仅限于一年中几个月的地区，因此用药次数不必超过三到四次。 SMC 可以进行适当干预的地区包括萨赫勒地区和萨赫勒以南地区的大部分地区（人口约 2 亿）。在季节性疟疾传播地区进行的研究表明，SMC 与磺胺多辛/乙胺嘧啶 (SP) 和阿莫地喹 (AQ) 组合可将严重和无并发症疟疾的发病率降低 70% 以上，并可能减少死亡人数。该干预措施安全、耐受性良好且成本效益高。乡村志愿者成功、安全地提供了抗疟疾药物。世界卫生组织政策咨询委员会最近审查了 SMC 的试验结果，并可能建议将其作为疟疾季节性传播严重地区的疟疾控制干预措施。尽管 SMC 配合 SP 和 AQ 在减少疟疾方面取得了成功，但试验中的儿童这次干预期间仍然遭受了许多传染病的袭击，有些严重，有些致命。这些严重疾病很可能大部分是由细菌感染引起的。因此，在 SMC 治疗方案中添加抗生素可能可以通过预防严重细菌感染来提供额外益处，从而减少严重疾病甚至死亡。最适合这种方式使用的抗生素是阿奇霉素 (AZ)。 AZ 已被广泛用于数百万健康儿童的治疗，以控制沙眼（一种可导致失明的细菌性眼部感染），并被证明是安全且耐受性良好的。令人惊讶的是，当 AZ 被部署到埃塞俄比亚的沙眼消除计划中时，总体儿童死亡率下降了约 65%。如果AZ确实可以预防幼儿死亡，那么它很可能是通过预防细菌感染，特别是由肺炎球菌引起的细菌感染来实现的，肺炎球菌是非洲幼儿死亡和严重疾病的重要原因。因此，在 SMC 方案中添加 AZ 可能会带来额外的益处，这在生物学上是合理的。为了验证这一假设，将在布基纳法索和马里疟疾传播严重地区的约 16,000 名儿童中进行试验。儿童将被随机分配接受含有 SP+AQ 的 SMC，添加或不添加 AZ。在整个 2013 年疟疾传播季节（7 月至 10 月），我们将仔细跟踪儿童。所有死亡或住院情况都将被记录，并记录因发热性疾病就诊的情况。在传播季节结束时，将对 4,000 名儿童随机抽取样本进行疟疾和贫血检查和检测。此时将测试疟原虫对 SP 的敏感性，以及从鼻子获得的肺炎球菌对 AZ 的敏感性。将确定在 SMC 方案中添加 AZ 的成本及其可接受性。该试验的结果应明确确定在用于 SMC 的 SP+AQ 方案中添加 AZ 是否会提供额外的益处，如果确实如此，这是否安全且具有成本效益。

项目成果

Additional file 4 of Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria

附加文件 4：布基纳法索和马里疟疾传播季节前幼儿的营养状况及其对临床疟疾发病率的影响

• DOI: http://dx.10.6084/m9.figshare.14826076
• 发表时间: 2021
• 作者: De Wit M

Additional file 2 of Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria

附加文件 2：布基纳法索和马里疟疾传播季节前幼儿的营养状况及其对临床疟疾发病率的影响

• DOI: http://dx.10.6084/m9.figshare.14826070
• 发表时间: 2021
• 作者: De Wit M

Effect of adding azithromycin to the antimalarials used for seasonal malaria chemoprevention on the nutritional status of African children.

在用于季节性疟疾化学预防的抗疟药中添加阿奇霉素对非洲儿童营养状况的影响。

• DOI: http://dx.10.1111/tmi.13390
• 发表时间: 2020
• 期刊: TM & IH
• 作者: Gore

Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria.

布基纳法索和马里疟疾传播季节前幼儿的营养状况及其对临床疟疾发病率的影响。

• DOI: http://dx.10.1186/s12936-021-03802-2
• 发表时间: 2021
• 期刊: Malaria journal
• 影响因子: 3
• 作者: De Wit M

Evaluation of seasonal malaria chemoprevention in two areas of intense seasonal malaria transmission: Secondary analysis of a household-randomised, placebo-controlled trial in Houndé District, Burkina Faso and Bougouni District, Mali.

对季节性疟疾传播强烈的两个地区的季节性疟疾化学预防的评估：对布基纳法索洪代区和马里布古尼区的家庭随机、安慰剂对照试验的二次分析。

• DOI: http://dx.10.1371/journal.pmed.1003214
• 发表时间: 2020
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Cairns ME