Pilgrim Africa, 8001 14th Avenue NE, Suite A, Seattle, WA, 98115, USA.
Makerere University College of Health Sciences, School of Public Health, P.O. Box 7072, Kampala, Uganda.
BMC Infect Dis. 2023 Feb 6;23(1):72. doi: 10.1186/s12879-023-07991-w.
Declines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC).
The 32-month quasi-experimental controlled before-and-after trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) of Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty at study start: MDA+IRS, IRS, SOC. IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round.
Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z = 9.6, p = 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5's (95% CI: [10.5%, 16.8%], Z = 4.02, p = 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z = 4.7, p = 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%, 83.0%], p = 0.0001) in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p < 0.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of study arms, the single large cluster per arm, and the lack of an MDA-only arm, considered to violate equipoise.
Despite being assessed at long time points 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Randomized trials of MDA in large areas undergoing IRS recommended as well as cohort studies of impact on incidence.
This trial was retrospectively registered 11/07/2018 with the Pan African Clinical Trials Registry (PACTR201807166695568).
乌干达疟疾负担的下降速度已经放缓。模型预测，当室内滞留喷洒（IRS）和大规模药物治疗（MDA）同时进行时，会产生协同作用。本研究调查了当 IRS 与 MDA 和标准治疗（SOC）相比，在 IRS 之外额外使用基于人群的 MDA 对疟疾发病率的任何额外保护作用。
这项为期 32 个月的准实验对照前后试验纳入了乌干达东北部卡塔奎区的一个开放队列居民（46765 人，第 1 次和 52133 人，第 4 次）。同意参与的参与者根据研究开始时的居住分区被分配到三个臂：MDA+IRS、IRS、SOC。IRS 使用甲基嘧啶和 MDA 使用青蒿琥酯-哌喹，每 8 个月进行 4 次同时进行的运动式回合。主要终点是疟疾的人群患病率，通过 6 项横断面调查估计，从基线开始，每 6 个月进行一次。
在所有 6 项调查中（意向治疗分析），将 MDA+IRS 和 IRS 臂中的疟疾患病率进行比较，在干预后大约每 6 个月，一个地质统计学模型发现 MDA 对所有年龄组的调整后的优势比（aOR）有显著的额外 15.5%（95%置信区间（CI）：[13.7%，17.5%]，Z=9.6，p=5e-20）下降，5 岁以下儿童的下降幅度为 13.3%（95% CI：[10.5%，16.8%]，Z=4.02，p=5e-5），儿童 5-15 岁的下降幅度为 10.1%（95% CI：[8.5%，11.8%]，Z=4.7，p=2e-5）。与 SOC 居民相比，MDA + IRS 臂的所有年龄段居民总体上对 qPCR 确诊疟疾的几率降低了 80.1%（95% CI：[80.0%，83.0%]，p=0.0001）。与基线相比，对不同时间点的二次差异分析显示 qPCR 阳性的 aOR（MDA+IRS 与 IRS）在 0.28 和 0.66 之间（p<0.001）。在 3 例严重不良事件中，有 1 例（非致命性）被认为与研究药物有关。局限性包括最初的非随机分组，每个臂的单个大簇，以及缺乏 MDA 单臂，这被认为违反了均衡。
尽管在干预后 5-7 个月的时间点进行了长时间的评估，但 IRS 加 MDA 比单独使用 IRS 提供了显著额外的疟疾感染保护。建议在进行 IRS 的大区域进行 MDA 的随机试验，并进行对发病率影响的队列研究。
该试验于 2018 年 11 月 7 日在泛非临床试验注册中心（PACTR201807166695568）进行了回顾性注册。
