Fig. 7: Potential impact of routinely testing for malaria during the first trimester.

a An illustration of the hypothesised mechanism by which the performance of standard RDTs are modified by gravidity. Women often experience chronic, asymptomatic parasitaemia outside of pregnancy which, as parasites are progressively cleared by the immune system, would eventually fall below the limit of detection of standard RDTs and be cleared if she had not conceived (grey line). If an asymptomatically infected woman becomes pregnant, and as her placenta develops so that maternal blood flows into the intervillous space (towards the end of the first trimester), the parasite undergoes antigenic switching, allowing it to bind to placental chondroitin sulfate A (CSA) receptors¹, multiplying to higher densities in women who have never experienced placental infection, leading to more severe and, due to higher concentrations of HRP2, more detectable infections (purple line). In subsequent pregnancies women mount a specific, acquired immune response, leading to better controlled, lower density and less detectable infection (turquoise and blue lines). b Shows a simulated example of the impact of testing and clearing infections at a first ANC visit at 10 weeks upon overall exposure to placental infection in primigravidae in a setting of EIR = 10 (ongoing peripheral infections are assumed to begin sequestering from the end of the first trimester onwards), simulations reflect our uncertainty in the sensitivity of the RDT at this time point, ranging from 26.8% (RDT sensitivity for asymptomatic infection in adults outside of pregnancy in such a setting based upon the relationship estimated in Wu et al.²²) to 90% (the approximate sensitivity of standard RDTs at first visit in areas of high transmission in primigravidae in ISTp trials). c Shows the proportional impact this screening would have upon the mean duration of placental infection either in the presence or absence of IPTp-SP (assuming low SP resistance) and by transmission intensity. d The impact upon the risk of LBW according to our model relationship between the duration and stage of placental infection and LBW⁵, two-thirds of these bars are coloured transparently emphasising our uncertainty in impact of IPTp-SP in terms of promoting catch-up growth³⁹.