Summary The surface protein Pfs47 mediates Plasmodium falciparum evasion of the Anopheles gambiae complement-like immune system. Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. falciparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae.

Key Points Question Are febrile neonates (in the first month of life) at higher risk for bacteremia and bacterial meningitis than febrile infants in their second month of life? Findings This systematic review and meta-analysis including 15 713 culture results from 12 studies found a significant difference in the prevalence of bacteremia (2.9%) and bacterial meningitis (1.2%) in febrile neonates vs the prevalence of bacteremia (1.6%) and bacterial meningitis (0.4%) in febrile infants in their second month of life. Meaning Febrile neonates may have roughly twice the rate of bacteremia and meningitis as febrile infants in their second month of life, although overall rates in both groups are low.

The most abundant form of estrogen circulating in fetal plasma is sulfoconjugated estrogen; for example, estradiol-3-sulfate (E2SO4) is more highly abundant than estradiol (E2). The present study investigated the ontogeny of the deconjugating (steroid sulfatase, STS) and conjugating (estrogen sulfotransferase, STF) in ovine fetal brain, and tested the hypothesis that treatment with E2SO4 would alter expression of one or both enzymes. STS was more highly expressed than STF, and both changed as a function of gestational age. E2SO4 infused intracerebroventricularly (icv) significantly increased plasma ACTH and cortisol concentrations. Plasma E2 and E2SO4 were increased, and brain expression of estrogen receptor alpha was decreased. STS and STF protein were up- and down-regulated, respectively. Pituitary POMC and FSH and hypothalamic CRH mRNA was decreased. We conclude that E2SO4 has complex actions on the fetal brain that might involve deconjugation by STS, but that the net result of direct E2SO4 icv infusion is more complex than can be accounted for by infusion of E2 alone.