Prevalence of Bacteremia and Bacterial Meningitis in Febrile Neonates and Infants in the Second Month of Life: A Systematic Review and Meta-analysis.

Importance: Febrile neonates (persons in the first month of life) are believed to be at higher risk for bacteremia or bacterial meningitis than infants in their second month of life. However, the true prevalence is unclear. Objective: To determine modern rates of bacteremia and bacterial meningitis in febrile neonates and infants in the second month of life presenting to an ambulatory setting. Data Sources: A comprehensive, no-limit search was conducted in PubMed using previously published search terms in February 2015 and repeated in September 2016. Study Selection: Abstracts and full texts were reviewed independently by several investigators. Studies were included if data regarding blood cultures or cerebrospinal fluid cultures from consecutive febrile infants in an ambulatory setting could be extrapolated within the age groups. To limit the analysis to the period after the availability of the Haemophilus influenzae type b vaccination, studies that collected data before 1990 were excluded. Data Extraction and Synthesis: Data were extracted in accordance with the Meta-analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines via independent abstraction by several investigators. The Newcastle-Ottawa Scale was used to assess bias. Main Outcomes and Measures: The primary outcomes were prevalence rates of bacteremia and bacterial meningitis in febrile neonates and infants in the second month of life. In neonates, prevalence rates were also estimated in the era of group B Streptococcus intrapartum antibiotic prophylaxis (after 1996). Results: In total, 7264 abstracts were screened, resulting in 188 full-text manuscripts reviewed, with 12 meeting inclusion criteria (with 15 713 culture results). For febrile neonates, the prevalence of bacteremia was 2.9% (95% CI, 2.3%-3.7%; I2 = 50%; n = 5145) and the prevalence of bacterial meningitis was 1.2% (95% CI, 0.8%-1.9%; I2 = 27%; n = 3288). In neonates in the era after group B Streptococcus prophylaxis, the prevalence of bacteremia was 3.0% (95% CI, 2.3%-3.9%; I2 = 6%; n = 2055) and the prevalence of meningitis was 1.0% (95% CI, 0.4%-2.1%; I2 = 28%; n = 1739). For febrile infants in the second month of life, the prevalence of bacteremia was 1.6% (95% CI, 0.9%-2.7%; I2 = 78%; n = 4778) and the prevalence of meningitis was 0.4% (95% CI, 0.2%-1.0%; I2 = 33%; n = 2502). Conclusions and Relevance: These findings suggest that febrile neonates have approximately twice the rate of bacteremia and meningitis as febrile infants in their second month of life.

The human malaria parasite Pfs47 gene mediates evasion of the mosquito 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.

Complex actions of estradiol-3-sulfate in late gestation fetal brain.

The most abundant form of estrogen circulating in fetal plasma is sulfo-conjugated estrogen; for example, estradiol-3-sulfate (E(2)SO(4)) is more highly abundant than estradiol (E(2)). The present study investigated the ontogeny of the deconjugating (steroid sulfatase [STS]) and conjugating (estrogen sulfotransferase [STF]) enzymes in ovine fetal brain and tested the hypothesis that treatment with E(2)SO(4) would alter the expression of one or both enzymes. Steroid sulfatase was more highly expressed than STF, and both changed as a function of gestational age. Estradiol-3-sulfate infused intracerebroventricularly (icv) significantly increased plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. Plasma E(2) and E(2)SO(4) were increased, and brain expression of estrogen receptor α was decreased. The proteins STS and STF were up- and downregulated, respectively. Pituitary proopiomelanocortin (POMC) and follicle-stimulating hormone (FSH) and hypothalamic corticotrophin-releasing hormone (CRH) messenger RNA (mRNA) was decreased. We conclude that E(2)SO(4) has complex actions on the fetal brain, which might involve deconjugation by STS, but that the net result of direct E(2)SO(4) icv infusion is more complex than can be accounted for by infusion of E(2) alone.