Abstract
SummaryBackgroundPrevention 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.MethodsWe 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.FindingsCompared 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.InterpretationOur 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.FundingMalaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Hygiene and Tropical Medicine.
Highlights
Malaria infection in pregnancy is associated with detrimental outcomes in the mother and the neonate, including foetal loss, low birthweight, maternal anaemia, and occasionally maternal or neonatal death.[1,2] In 2007, an estimated 30 million pregnancies occurred in the WHO African region in areas where Plasmodium falciparum is endemic.[3]
For the child health outcomes, stillbirth and neonatal death were better with IPTp-DP3, but low birthweight was marginally better in the IPTp-SP3 group
The negative disability-adjusted life-years (DALYs) can be attributed to a small, nonsignificant increase in child mortality outcomes in both IPTp-DP groups in the Uganda-I trial, which was a small trial (n=300) with insufficient statistical power to detect a difference in mortality outcomes
Summary
Malaria infection in pregnancy is associated with detrimental outcomes in the mother and the neonate, including foetal loss, low birthweight, maternal anaemia, and occasionally maternal or neonatal death.[1,2] In 2007, an estimated 30 million pregnancies occurred in the WHO African region in areas where Plasmodium falciparum is endemic.[3]. WHO currently recommends insecticidal nets combined with monthly www.thelancet.com/lancetgh Vol 8 December 2020 e1512. Evidence before this study Monthly administration of intermittent preventive treatment in pregnancy with sulfadoxine–pyrimethamine (IPTp-SP) is recommended by WHO to prevent malaria in HIV-negative women. Three trials of intermittent preventive treatment in pregnancy with dihydroartemisinin–piperaquine (IPTp-DP) were done in areas of high resistance to sulfadoxine– pyrimethamine, one in Kenya and two in Uganda. These trials compared IPTp-DP with IPTp-SP using different combinations of three doses or monthly administration of either drug combination. IPTp-DP was well tolerated, effective, and acceptable, suggesting that dihydroartemisinin– piperaquine is a promising preventive treatment candidate. To our knowledge, no cost-effectiveness analysis has been done to date
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