Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) and SP plus azithromycin (SPAZ) reduces low birthweight (<2,500 g) in women without malarial and reproductive tract infections. This study investigates the impact of SPAZ on associations between plasma biomarkers of inflammation and angiogenesis and adverse pregnancy outcomes in 2,012 Papua New Guinean women. Concentrations of C-reactive protein (CRP), α-1-acid glycoprotein (AGP), soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at enrolment and delivery in a trial comparing SPAZ to SP plus chloroquine (SPCQ). At antenatal enrolment higher CRP (adjusted odds ratio 1.52; 95% confidence interval [CI] 1.03–2.25), sEng (4.35; 1.77, 10.7) and sFlt1 (2.21; 1.09, 4.48) were associated with preterm birth, and higher sEng with low birthweight (1.39; 1.11,3.37), in SPCQ recipients only. Increased enrolment sFlt1:PlGF ratios associated with LBW in all women (1.46; 1.11, 1.90). At delivery, higher AGP levels were strongly associated with low birthweight, preterm birth and small-for-gestational age babies in the SPCQ arm only. Restricting analyses to women without malaria infection did not materially alter these relationships. Women receiving SPAZ had lower delivery AGP and CRP levels (p < 0.001). SPAZ may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection.
Malaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.
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