Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

Objectives  To evaluate persistence of several Plasmodium antigens in pregnant women after treatment and compare diagnostics during treatment follow‐up. Methods  Thirty‐two pregnant women (N = 32) with confirmed malaria infection by a histidine‐rich protein 2 (HRP2)‐based rapid diagnostic test (RDT) and microscopy were followed for 28 days after artemisinin‐based combination therapy (ACT). A Plasmodium lactate dehydrogenase (pLDH)‐based RDT and two ELISAs based on the detection of dihydrofolate reductase–thymidylate synthase (DHFR‐TS) and haeme detoxification protein (HDP) were compared with each other and to RT‐PCR at each visit. Results  The mean visit number (95% confidence interval) on which the HRP2‐based RDT was still positive after treatment was 3.4 (2.7–4.1) visits with some patients still positive at day 28. This is significantly later than the pLDH‐based RDT [0.84 (0.55–1.1)], microscopy (median 1, range 1–3), DHFR‐TS‐ELISA [1.7 (1.1–2.3)] and RT‐PCR (median 2, range 1–5) (P < 0.05), but not significantly later than HDP‐ELISA [2.1 (1.6–2.7)]. Lower gravidity and higher parasite density at day 0 resulted in significantly longer positive results with most tests (P < 0.05). Conclusions  HRP2 can persist up to 28 days after ACT treatment; therefore, this test is not suitable for treatment follow‐up in pregnant women and can generate problems when using this test during intermittent preventive treatment (IPTp). DHFR‐TS is less persistent than HRP2, making it a potentially interesting target for diagnosis.

NCT01941264; ISRCTN37259296.

Abstract.One of the current strategies to prevent malaria in pregnancy is intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). However, in order for pregnant women to receive an adequate number of SP doses, they should attend a health facility on a regular basis. In addition, SP resistance may decrease IPTp-SP efficacy. New or additional interventions for preventing malaria during pregnancy are therefore warranted. Because it is known that community health workers (CHWs) can diagnose and treat malaria in children, in this study screening and treatment of malaria in pregnancy by CHWs was evaluated as an addition to the regular IPTp-SP program. CHWs used rapid diagnostic tests (RDTs) for screening and artemether-lumefantrine was given in case of a positive RDT. Overall, CHWs were able to conduct RDTs with a sensitivity of 81.5% (95% confidence interval [CI] 67.9-90.2) and high specificity of 92.1% (95% CI 89.9-93.9) compared with microscopy. After a positive RDT, 79.1% of women received artemether-lumefantrine. When treatment was not given, this was largely due to the woman being already under treatment. Almost all treated women finished the full course of artemether-lumefantrine (96.4%). In conclusion, CHWs are capable of performing RDTs with high specificity and acceptable sensitivity, the latter being dependent on the limit of detection of RDTs. Furthermore, CHWs showed excellent adherence to test results and treatment guidelines, suggesting they can be deployed for screen and treat approaches of malaria in pregnancy.BACKGROUND

BackgroundPregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied.MethodsBlood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used.ResultsThe prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking.ConclusionThe high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1831-y) contains supplementary material, which is available to authorized users.