The unanticipated benefits of protecting young children from malaria.
The unanticipated benefits of protecting young children from malaria.
复制标题
保护幼儿免受疟疾的意想不到的好处。
DOI：
10.1016/s1473-3099(19)30285-3
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Laufer,MiriamK
中科院分区：
文献类型：
--
作者：
Cohee,LaurenM;Laufer,MiriamK
撒哈拉以南非洲的幼儿占全世界疟疾相关死亡人数的大多数。每次提出一项新的干预措施来保护这一人群时，研究和政策界都表示担心，严重疾病的负担将转移到不再受到干预措施保护的年龄较大的儿童身上。这种情况被称为反弹，而不仅仅是一个理论上的问题。在扩大疟疾控制干预措施的背景下，过去20年在肯尼亚和冈比亚进行的大型回顾性研究表明，疾病分布发生了流行病学变化，即临床疟疾的平均年龄随着传播的减少而增加。1，2然而，正如玛丽穆欣多及其同事在《柳叶刀传染病》杂志上的试验3中所强调的，评估幼儿有针对性干预后疟疾反弹的研究结果不一致，疟疾反弹的特征仍然很差。在生命的前2年预防疟疾对随后的疟疾感染和疾病的影响是Muhindo及其同事的一个关键发现。作者报告了一项双盲、随机、对照的2期试验的结果，在该试验中，他们为8周至24个月的乌干达儿童提供了双氢青蒿素-哌喹间歇性预防治疗（IPT），每4周或12周一次。他们评估了干预期间和停止干预后1年内有症状疟疾的发生率，以检测反弹。正如在这种高传播环境中所预期的那样，研究人员表明，在干预期间，与每12周治疗一次相比，每4周治疗一次使症状性疟疾的发病率降低了96%（校正发病率比[aIRR] 0· 041，95% CI 0· 012-0· 150，p< 0· 0001）。重要的是，这种保护似乎在治疗后的一年中继续存在：以前接受过每4周一次双氢青蒿素-哌喹IPT的儿童比每12周一次接受双氢青蒿素-哌喹的儿童症状性疾病的发生率低38%（aIRR 0.62，0.40 - 0.95，p= 0.028）。虽然持续保护的发现是有希望的，但该研究在评估反弹方面存在重要局限性。试验中未纳入对照组，因为之前在该研究中心证实了IPT在该年龄组中的获益。因此，尽管不太可能，但不能排除两个治疗组的疾病发生率高于未接受干预的儿童的可能性。在更频繁的治疗后继续提供保护的拟议机制是，双氢青蒿素-哌喹可保护儿童免受血液期疟疾感染，但不能防止接触对免疫力发展至关重要的红细胞前期寄生虫;接受双氢青蒿素IPT的儿童-哌喹每4周继续被感染的蚊子叮咬，并在肝脏内发生感染，但免受致病血液的影响，通过双氢青蒿素-哌喹连续化学预防对寄生虫进行分期。活动性血液阶段感染也可能干扰有效免疫应答的获得。[4] Muhindo及其同事没有讨论的这一策略的另一个好处是，这些儿童也不太可能感染包括配子体阶段在内的感染，这是人-蚊子寄生虫传播和感染周期延续所需的寄生虫阶段。以前的研究5每月双氢青蒿素-哌喹治疗在这种情况下…
Young children in sub-Saharan Africa account for the majority of malaria-associated deaths worldwide. Every time a new intervention is proposed to protect this population, the research and policy communities voice the concern that the burden of severe disease will shift to older children who are no longer protected by the intervention. This situation is referred to as rebound and is not merely a theoretical concern. In the context of scaling up malaria control interventions, over the past two decades large retrospective studies in Kenya and The Gambia showed an epidemiological shift in the distribution of disease—ie, the mean age of clinical malaria increased as transmission declined. 1, 2 However, as Mary Muhindo and colleagues highlight in their trial3 in The Lancet Infectious Diseases, results of studies evaluating rebound malaria after targeted interventions in young children have been inconsistent and rebound malaria remains poorly characterised. The impact of preventing malaria during the first 2 years of life on subsequent malaria infection and disease is a key finding addressed by Muhindo and colleagues. The authors report the results of a doubleblind, randomised, controlled phase 2 trial in which they provided intermittent preventive treatment (IPT) with dihydroartemisinin–piperaquine to Ugandan children from age 8 weeks to 24 months either every 4 or 12 weeks. They assessed the incidence of symptomatic malaria during the intervention and up to 1 year after cessation of the intervention to detect rebound. As expected in this high transmission setting, the investigators showed that during the intervention, treatment every 4 weeks reduced the incidence of symptomatic malaria by 96% compared with treatment every 12 weeks (adjusted incidence rate ratio [aIRR] 0· 041, 95% CI 0· 012–0· 150, p< 0· 0001). Importantly, this protection seemed to continue in the year following treatment: children who had previously received IPT with dihydroartemisinin–piperaquine every 4 weeks had a 38% lower incidence of symptomatic disease than children who had received dihydroartemisinin–piperaquine every 12 weeks (aIRR 0· 62, 0· 40–0· 95, p= 0· 028). Although the finding of sustained protection is promising, the study has an important limitation with regard to the assessment of rebound. No control group was included in the trial, because of the previously demonstrated benefit of IPT in this age group at this site. Thus, although unlikely, the possibility that the incidence of disease in both treatment groups was higher than in children who had not received the intervention cannot be excluded. The proposed mechanism of continued protection following more frequent treatment is that dihydroartemisinin–piperaquine protects children from bloodstage malaria infection, but does not prevent exposure to pre-erythrocytic stage parasites that are important for the development of immunity; children who received IPT with dihydroartemisinin–piperaquine every 4 weeks continued to be bitten by infected mosquitos and develop infections within the liver but were protected from disease-causing blood-stage parasites by continuous chemoprophylaxis with dihydroartemisinin–piperaquine. Active blood-stage infection might also interfere with the acquisition of an effective immune response. 4 An additional benefit of this strategy, not discussed by Muhindo and colleagues, is that these children are also unlikely to have infections that include the gametocyte stage, which is the parasitic stage required for human-to-mosquito parasite transmission and perpetuation of the cycle of infection. Previous studies5 of monthly dihydroartemisinin–piperaquine treatment in this setting …
影响因子：
6.4
作者：
Jagannathan, Prasanna;Bowen, Katherine;Feeney, Margaret E.
通讯作者：
Feeney, Margaret E.
影响因子：
56.3
作者：
Muhindo, Mary K.;Jagannathan, Prasanna;Kamya, Moses R.
通讯作者：
Kamya, Moses R.