Faculty of Public Health and Policy, Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK.
Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
Lancet Glob Health. 2020 Dec;8(12):e1512-e1523. doi: 10.1016/S2214-109X(20)30369-7. Epub 2020 Oct 30.
Prevention of malaria infection during pregnancy in HIV-negative women currently relies on the use of long-lasting insecticidal nets together with intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Increasing sulfadoxine-pyrimethamine resistance in Africa threatens current prevention of malaria during pregnancy. Thus, a replacement for IPTp-SP is urgently needed, especially for locations with high sulfadoxine-pyrimethamine resistance. Dihydroartemisinin-piperaquine is a promising candidate. We aimed to estimate the cost-effectiveness of intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) versus IPTp-SP to prevent clinical malaria infection (and its sequelae) during pregnancy.
We did a cost-effectiveness analysis using meta-analysis and individual trial results from three clinical trials done in Kenya and Uganda. We calculated disability-adjusted life-years (DALYs) arising from stillbirths, neonatal death, low birthweight, mild and moderate maternal anaemia, and clinical malaria infection, associated with malaria during pregnancy. Cost estimates were obtained from data collected in observational studies, health-facility costings, and from international drug procurement databases. The cost-effectiveness analyses were done from a health-care provider perspective using a decision tree model with a lifetime horizon. Deterministic and probabilistic sensitivity analyses using appropriate parameter ranges and distributions were also done. Results are presented as the incremental cost per DALY averted and the likelihood that an intervention is cost-effective for different cost-effectiveness thresholds.
Compared with three doses of sulfadoxine-pyrimethamine, three doses of dihydroartemisinin-piperaquine, delivered to a hypothetical cohort of 1000 pregnant women, averted 892 DALYs (95% credibility interval 274 to 1517) at an incremental cost of US$7051 (2653 to 13 038) generating an incremental cost-effectiveness ratio (ICER) of $8 (2 to 29) per DALY averted. Compared with monthly doses of sulfadoxine-pyrimethamine, monthly doses of dihydroartemisinin-piperaquine averted 534 DALYS (-141 to 1233) at a cost of $13 427 (4994 to 22 895), resulting in an ICER of $25 (-151 to 224) per DALY averted. Both results were highly robust to most or all variations in the deterministic sensitivity analysis.
Our findings suggest that among HIV-negative pregnant women with high uptake of long-lasting insecticidal nets, IPTp-DP is cost-effective in areas with high malaria transmission and high sulfadoxine-pyrimethamine resistance. These data provide a comprehensive overview of the current evidence on the cost-effectiveness of IPTp-DP. Nevertheless, before a policy change is advocated, we recommend further research into the effectiveness and costs of different regimens of IPTp-DP in settings with different underlying sulfadoxine-pyrimethamine resistance.
Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Hygiene and Tropical Medicine.
目前,在 HIV 阴性妇女中预防疟疾感染依赖于使用长效驱虫蚊帐和在妊娠期间间歇性预防治疗(IPTp-SP)。在非洲,磺胺多辛-乙胺嘧啶的耐药性不断增加,这对目前的妊娠期间疟疾预防构成了威胁。因此,迫切需要一种替代药物,尤其是在磺胺多辛-乙胺嘧啶耐药性较高的地区。二氢青蒿素-哌喹是一种很有前途的候选药物。我们旨在评估在妊娠期间间歇性预防治疗使用二氢青蒿素-哌喹(IPTp-DP)替代磺胺多辛-乙胺嘧啶(IPTp-SP)预防妊娠期间临床疟疾感染(及其后遗症)的成本效益。
我们使用荟萃分析和在肯尼亚和乌干达进行的三项临床试验的个体试验结果进行了成本效益分析。我们计算了因疟疾引起的死产、新生儿死亡、低出生体重、轻度和中度产妇贫血以及临床疟疾感染而导致的残疾调整生命年(DALYs)。成本估算来自观察性研究、医疗机构成本核算以及国际药物采购数据库中的数据。成本效益分析从医疗保健提供者的角度出发,使用具有终生视野的决策树模型进行。还使用适当的参数范围和分布进行了确定性和概率敏感性分析。结果以每避免一个 DALY 的增量成本和干预措施在不同成本效益阈值下具有成本效益的可能性表示。
与三剂磺胺多辛-乙胺嘧啶相比,在一个 1000 名孕妇的假设队列中使用三剂二氢青蒿素-哌喹,可以避免 892 个 DALYs(95%置信区间 274 至 1517),增量成本为 7051 美元(2653 至 13038 美元),增量成本效益比(ICER)为每避免一个 DALY 8 美元(2 至 29 美元)。与每月一剂磺胺多辛-乙胺嘧啶相比,每月一剂二氢青蒿素-哌喹的成本为 13427 美元(4994 至 22895 美元),可避免 534 个 DALYs(-141 至 1233),ICER 为每避免一个 DALY 25 美元(-151 至 224)。这两个结果在确定性敏感性分析的大多数或所有变化中都非常稳健。
我们的研究结果表明,在采用长效驱虫蚊帐覆盖率高的 HIV 阴性孕妇中,在疟疾传播率高和磺胺多辛-乙胺嘧啶耐药率高的地区,IPTp-DP 具有成本效益。这些数据提供了关于 IPTp-DP 的成本效益的当前证据的综合概述。然而,在提倡政策变化之前,我们建议进一步研究在不同磺胺多辛-乙胺嘧啶耐药性背景下不同 IPTp-DP 方案的有效性和成本。
疟疾妊娠联盟,该联盟由比尔及梅琳达·盖茨基金会向利物浦热带医学院提供赠款资助。