Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia

Abstract

Background: In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting lowdensity infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women. Methods: A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing. Results: The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/μL). Conclusions: There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated.

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 ].…”

“…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 ].…”

“…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 ]. Furthermore, given its high negative predictive value, malaria LAMP can rule out malaria infection making it a cost-effective alternative for screening of returning febrile travelers [ 30 , 34 , 83 ].…”

Detection of Falciparum Malaria Imported From Africa With a Highly Specific and Sensitive Loop-Mediated Isothermal Amplification (LAMP) Assay

“…Previous work established LAMP as more sensitive than microscopyor RDT to detect low-parasitemia infections (13)(14)(15)(16)(17)(18)(23)(24)(25)(26), but some showed negative results (10,(27)(28)(29). Assays targeting 18srRNA (13)(14)(15)(16)(17)(18)30) achieve sensitivity and speci city matching or exceeding PCR.…”