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Background Malaria in pregnancy is associated with adverse birth outcomes. However, the underlying mechanisms remain poorly understood. Tight regulation of angiogenic, metabolic, and inflammatory pathways are essential for healthy pregnancies. We hypothesized that malaria disrupts these pathways leading to preterm birth (PTB). Methods and findings We conducted a secondary analysis of a randomized trial of malaria prevention in pregnancy conducted in Malawi from July 21, 2011, to March 18, 2013. We longitudinally assessed circulating mediators of angiogenic, metabolic, and inflammatory pathways during pregnancy in a cohort of HIV-negative women (n = 1,628), with a median age of 21 years [18, 25], and 562 (35%) were primigravid. Pregnancies were ultrasound dated, and samples were analyzed at 13 to 23 weeks (Visit 1), 28 to 33 weeks (Visit 2), and/or 34 to 36 weeks (Visit 3). Malaria prevalence was high; 70% (n = 1,138) had PCR-positive Plasmodium falciparum infection at least once over the course of pregnancy and/or positive placental histology. The risk of delivering preterm in the entire cohort was 20% (n = 304/1506). Women with malaria before 24 weeks gestation had a higher risk of PTB (24% versus 18%, p = 0.005; adjusted relative risk [aRR] 1.30, 95% confidence interval [CI] 1.04-1.63, p = 0.021); and those who were malaria positive only before week 24 had an even greater risk of PTB (28% versus 17%, p = 0.02; with an aRR of 1.67, 95% CI 1.20-2.30, p = 0.002). Using linear mixed-effects modeling, malaria before 24 weeks gestation was associated with altered kinetics of inflammatory (C-Reactive Protein [CRP], Chitinase 3-like protein-1 [CHI3L1], Interleukin 18 Binding Protein [IL-18BP], soluble Tumor Necrosis Factor receptor II [sTNFRII], soluble Intercellular Adhesion Molecule-1 [sICAM-1]), angiogenic (soluble Endoglin [sEng]), and metabolic mediators (Leptin, Angiopoietin-like 3 [Angptl3]) over the course of pregnancy (X.sup.2 > 13.0, p [less than or equal to] 0.001 for each). Limitations include being underpowered to assess the impact on nonviable births, being unable to assess women who had not received any antimalarials, and, because of the exposure to antimalarials in the second trimester, there were limited numbers of malaria infections late in pregnancy. Conclusions Current interventions for the prevention of malaria in pregnancy are initiated at the first antenatal visit, usually in the second trimester. In this study, we found that many women are already malaria-infected by their first visit. Malaria infection before 24 weeks gestation was associated with dysregulation of essential regulators of angiogenesis, metabolism, and inflammation and an increased risk of PTB. Preventing malaria earlier in pregnancy may reduce placental dysfunction and thereby improve birth outcomes in malaria-endemic settings., Author(s): Robyn E. Elphinstone 1, Andrea M. Weckman 1, Chloe R. McDonald 1, Vanessa Tran 1, Kathleen Zhong 1, Mwayiwawo Madanitsa 2, Linda Kalilani-Phiri 2, Carole Khairallah 3, Steve M. [...]

Research has been conducted on the ferriprotoporphyrin IX heme mu-oxo dimers and aminoquinolinal antimalarial drugs. The solution structures formed between these compounds at different pH have been investigated via the use of paramagnetic relaxation effects in determining the distance constraints for these solution structures and the details are reported.

Research has been conducted on the substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones. The results of their synthesis and the study of their antimalarial and anticancer activity are presented.

Research has been conducted on the intraerythrocytic malaria parasite. The parasiticidal events taking place within this parasite have been analyzed and the theories concerning the qinghaosu (artemisinin) antimalarial mechanism have been discussed.

Research has been conducted on the manganese(II) tetraphenylporphyrin, an antimalarial drug with a heme model. The reactivity of the trioxane molecules related structurally to this drug has been tested and the results indicate that alkylation is the pharmacological activity factor of this drug.

Research has been conducted on the antimalarial beta-sulfonyl endoperoxides. The results of the reactions of these antimalarial beta-sulfonyl endoperoxides with the iron(II) salts are described.

Research has been conducted on the insect pathogenic fungus Cordyceps nipponica extracts fractination of which led to N-hydroxy- and N-methoxy-2-pyridones isolation. The structures of these compounds have been determined via spectroscopic methods, chemical conversions and single-crystal X-ray diffraction analyses.

The human malarial parasite Plasmodium falciparum has become resistant to the antimalarial drug chloroquine, resulting in a dramatic increase in the incidence of malaria worldwide. An understanding of the parasite's biology could provide a basis for the development of new, improved antimalarial drugs. A new study identifies and characterizes a physiological marker linked to the chloroquine-resistant (CQR) Plasmodium falciparum. It is shown that CQR parasites constantly exhibit elevated cytoplasmic pH against that of chloroquine-sensitive strains. It is suggested that chloroquine activates the plasma membrane protein, Na+/H+ exchanger, involved in cell volume regulation and cytoplasmic pH.

The two modes of self-destruction at the cellular level--apoptosis (self-killing) and autophagy (self-eating)--are thought to be tumor suppressive. In particular, germline loss of function of genes involved in autophagy has been associated with tumorigenesis. However, recent studies, including the one by Maclean et al. reported in this issue of the JCI, indicate that autophagy can provide a means for cell survival when nutrients are limiting, such that inhibition of autophagy by the antimalarial drug chloroquine can inhibit tumorigenesis, specifically Myc-induced lymphoma in mice (see the related article beginning on page 79). These findings suggest that a new use of an old drug for cancer prevention may profoundly affect disease outcome., Burkitt lymphoma occurs endemically in Africa, sporadically elsewhere, and in association with HIV/AIDS worldwide. Endemic Burkitt lymphoma, a high-proliferative-index (high-growth-rate) B cell malignancy initially described in 1958 by Denis Burkitt, [...]

The principal malaria parasite, Plasmodium falciparum, develops resistance to three first-line antimalarial drugs when mutations occur in just one gene, say researchers in Australia. Moreover, resistance to a fourth and [...]

Two patients previously treated with azathioprine and anti-malarials without effect were subsequently treated with MMF 2 g daily. Skin lesions cleared on this regimen and one patient was in remission [...]