Use of a highly-sensitive rapid diagnostic test to screen for malaria in pregnancy in Indonesia

Abstract

Background: The sensitivity of rapid diagnostic tests (RDTs) for malaria is inadequate for detecting low-density, often asymptomatic infections, such as those that can occur when screening pregnant women for malaria. The performance of the Alere ™ Ultra-sensitive Malaria Ag Plasmodium falciparum RDT (uRDT) was assessed retrospectively in pregnant women in Indonesia. Methods:The diagnostic performance of the uRDT and the CareStart ™ Malaria HRP2/pLDH VOM (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) Combo RDT (csRDT) were assessed using 270 stored red blood cell pellets and plasma samples from asymptomatic pregnant women. These included 112 P. falciparum negative and 158 P. falciparum positive samples detected by a composite test (qPCR, LAMP, nPCR) as reference standard. Diagnostic indicators: sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), diagnostic odds ratio (DOR) and the level of agreement (kappa) were calculated for comparison. Results:Compared with the reference test, the uRDT had a sensitivity of 19.6% (95% CI 13.9-26.8) and specificity of 98.2% (93.1-99.7%). The csRDT was 22.8% (16.7-30.3) sensitive and 95.5% (89.4-98.3) specific for P. falciparum infections. Performance of the uRDT was non-significantly different to the csRDT (p = 0.169). RDT outcome was stratified by qPCR cycling threshold (Ct), and performance of the RDTs was found to be comparable across parasite loads. Conclusion:The uRDT performed similarly to the currently used csRDTs in detecting P. falciparum infections in asymptomatic pregnant women. In these settings, molecular diagnostics are currently the most sensitive for malaria. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.…”

Diagnostic performance of an ultrasensitive HRP2-based malaria rapid diagnostic test kit used in surveys of afebrile people living in Southern Ghana

“…A previous study in pregnant women from a moderate malaria transmission site in Colombia identified a slightly higher sensitivity of the UsmRDT over the standard RDT (85.7% versus 82.8%), but similar specificity (> 99.0%) [ 23 ]. Using archived blood samples from pregnant women from a low transmission setting in Indonesia, a study reported no difference in performance of the UsmRDT relative to the standard CareStart combo-RDT kit [ 24 ]. These contrasting reports present the need to provide more evidence on the performance of the UsmRDT against standard malaria RDT kits to influence policies relating to malaria diagnostics.…”

Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique

“…Overall, these results raise the question of the added value of the uRDTs evaluated in this study, in Mozambique. In fact, the utility of these uRDTs remains unclear, partly as a result of the emergent body of evidence in line with the performance outcomes presented here [21,26,27,29]. In summary, three main use-cases have been proposed for this diagnostic tool: (1) To be used in malaria elimination contexts to more accurately measure prevalence or guide test-and-treat strategies to interrupt malaria transmission in the community, (2) for improved case management, and 3) to detect low-density infections among pregnant women.…”

“…Similarly, studies conducted among pregnant women observed a higher performance of uRDTs among afebrile women compared to febrile ones [28,30]. These studies were conducted under laboratory conditions using retrospectively collected samples [28][29][30]. However, there is currently no evidence of the performance of uRDTs among pregnant women when the tests are directly conducted at point of care.…”

“…Studies evaluating the potential role of uRDTs in case management found no differences in the performance of uRDTs and cRDTs for clinical malaria diagnosis among non-pregnant patients [27]. Finally, a similar or higher performance of uRDTs compared to cRDTs has been reported in pregnant women when tested using retrospectively collected peripheral or placental blood samples [28][29][30].…”