模拟婴幼儿间歇性预防治疗疟疾的替代给药方案的保护效果。

BACKGROUND

Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy.

METHODS AND FINDINGS

A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone.

CONCLUSION

Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria.

背景

间歇性预防治疗在婴儿中（IPTi）用磺胺多辛-乙胺嘧啶（SP）是由世界卫生组织推荐的，在婴儿期疟疾发病率高且 SP 耐药率低的地方。目前的输送策略是通过常规扩大免疫规划联系在婴儿期（EPI-IPTi）。然而，在疟疾传播具有季节性的地方，或者疟疾负担主要不在婴儿期的地方，这种方法可能会有所改进。

方法和发现

我们开发了一个数学模型来估计 IPT 对 2-24 个月儿童临床疟疾的保护效力（PE），使用来自加纳纳瓦罗尼奥 EPI-IPTi 试验的昆虫学和流行病学数据来参数化模型。季节性靶向 IPT 在婴儿中的保护（sIPTi）、季节性 IPT 在儿童中的保护（sIPTc）和用长效青蒿素联合疗法（LA-ACTs）进行病例管理的保护效果被预测用于纳瓦罗尼奥和具有不同传播强度和季节性的地点。在纳瓦罗尼奥，sIPTi 的预测 PE 在 24 个月时为 26%，而 EPI-IPTi 为 16%。所有 2 岁以下儿童的 sIPTc 会在 24 个月时提供 52%的 PE。季节性靶向 IPT 在各种传播模式下仍然具有优势。在某些情况下，LA-ACTs 用于病例管理可能会提供与 EPI-IPTi 相似的保护。然而，EPI-IPTi 或 sIPT 联合 LA-ACTs 将比单独使用任何一种策略更具保护作用。

结论

通过 EPI 向婴儿提供 IPT 的效果不佳，因为在疟疾风险最高的时候个体不能得到 IPT 的保护，而且年长儿童也不能得到保护。在季节性传播或疟疾负担超出婴儿期的地方，需要替代 EPI 的输送策略。长效 ACTs 也可能显著降低疟疾发病率。然而，必须开发输送系统，以确保两种形式的化学预防都能到达最易受疟疾感染的个体。