Active case detection of malaria in pregnancy using loop-mediated amplification (LAMP): a pilot outcomes study in South West Ethiopia

Abstract

Background: 125 million women are pregnant each year in malaria endemic areas and are, therefore, at risk of Malaria in Pregnancy (MiP). MiP is the direct consequence of Plasmodium infection during pregnancy. The sequestration of Plasmodium falciparum parasites in the placenta adversely affects fetal development and impacts newborn birth weight. Importantly, women presenting with MiP commonly develop anaemia. In Ethiopia, the Ministry of Health recommends screening symptomatic women only at antenatal care visits with no formal intermittent preventive therapy. Since MiP can display low-level parasitaemia, current tests which include microscopy and RDT are challenged to detect these cases. Loop mediated isothermal Amplification (LAMP) technology is a highly sensitive technique for DNA detection and is field compatible. This study aims to evaluate the impact of active malaria case detection during pregnancy using LAMP technology in terms of birth outcomes. Methods: A longitudinal study was conducted in two health centres of the Kafa zone, South West Ethiopia. Both symptomatic and asymptomatic pregnant women were enrolled in the first or second trimester and allocated to either Standard of Care (SOC-microscopy and RDT) or LAMP (LAMP, microscopy and RDT). Women completed at least three visits prior to delivery, and the patient was referred for treatment if Plasmodium infection was detected by any of the testing methods. The primary outcome was to measure absolute birth weight, proportion of low birth weight, and maternal/neonatal haemoglobin in each arm. Secondary outcomes were to assess the performance of microscopy and RDT versus LAMP conducted in the field. Results: One hundred and ninety-nine women were included and assigned to either LAMP or SOC. Six were lost to follow up. In this cohort, 66.8% of women did not display any clinical symptoms and 70.9% were multi-parous. A reduced proportion of low birth weight newborns was observed in the LAMP group (0%) compared to standard of care (14%) (p <0.001). Improved neonatal haemoglobin was observed in the LAMP (13.1 g/dL) versus the SOC (12.8 g/ dL) (p = 0.024) arm. RDT and microscopy had an analytical sensitivity of 66.7% and 55.6% compared to LAMP as a reference standard.

Performance and Application of Commercially Available Loop-Mediated Isothermal Amplification (LAMP) Kits in Malaria Endemic and Non-Endemic Settings

“…LAMP has shown to greatly improve the detection of these low-density infections in maternal peripheral blood during pregnancy [ 70 , 73 , 74 , 75 , 76 , 77 ] as well as in placental blood at delivery [ 77 , 78 , 79 ], when compared to microscopy, and conventional or highly sensitive RDTs ( Table 4 ). The fact that antenatal care is usually provided in clinics where the basic laboratory procedures can easily be conducted, together with the improved sensitivity for the diagnosis of gestational and placental malaria [ 70 , 74 , 75 , 77 ], suggests that LAMP could provide a valuable tool in the screening of malaria during antenatal visits or at delivery. However, the relevance of detecting and treating sub-patent malaria infections in pregnant women, and the impact this may have on birth outcomes, needs to be further evaluated in larger studies [ 54 , 75 ].…”

“…The fact that antenatal care is usually provided in clinics where the basic laboratory procedures can easily be conducted, together with the improved sensitivity for the diagnosis of gestational and placental malaria [ 70 , 74 , 75 , 77 ], suggests that LAMP could provide a valuable tool in the screening of malaria during antenatal visits or at delivery. However, the relevance of detecting and treating sub-patent malaria infections in pregnant women, and the impact this may have on birth outcomes, needs to be further evaluated in larger studies [ 54 , 75 ]. In addition, the commercially available LAMP kits are currently retailing at a higher cost-per-test than RDT and microscopy, potentially limiting their use in low and middle-income malaria endemic countries [ 75 , 77 ].…”

“…However, the relevance of detecting and treating sub-patent malaria infections in pregnant women, and the impact this may have on birth outcomes, needs to be further evaluated in larger studies [ 54 , 75 ]. In addition, the commercially available LAMP kits are currently retailing at a higher cost-per-test than RDT and microscopy, potentially limiting their use in low and middle-income malaria endemic countries [ 75 , 77 ]. Even with an affordable LAMP test, switching strategies to screening with LAMP may face additional operational and financial difficulties [ 75 ].…”

“…In addition, the commercially available LAMP kits are currently retailing at a higher cost-per-test than RDT and microscopy, potentially limiting their use in low and middle-income malaria endemic countries [ 75 , 77 ]. Even with an affordable LAMP test, switching strategies to screening with LAMP may face additional operational and financial difficulties [ 75 ]. Consequently, further studies are needed to evaluate the cost-effectiveness of the potential integration of LAMP into maternal health programs in different transmission settings [ 70 , 77 ].…”

“…Although LAMP in its current form and cost is unlikely to become a reality for point-of-care diagnosis of clinically symptomatic malaria in low resource settings [ 1 , 9 , 33 , 44 ], it could improve the detection and management of malaria early on in pregnancy by incorporating LAMP screening into antenatal care programs where IPTp is not implemented [ 70 , 74 , 75 , 77 ]. However, the impact that detecting and treating sub-patent P. falciparum infections in pregnant women might have on adverse birth outcomes requires further evaluation [ 73 , 80 , 81 ], together with thorough assessment of the cost effectiveness of the integration of LAMP as a tool for malaria screening during pregnancy in different transmission settings [ 70 , 77 ].…”