Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

Hormone Therapy and Young-Onset Breast Cancer

Estrogen plus progestin hormone therapy (HT) is associated with an increased risk of postmenopausal breast cancer, but few studies have examined the impact of HT use on the risk of breast cancer in younger women. We assessed the association between estrogen plus progestin HT or unopposed estrogen HT and young-onset breast cancer using data from the Two Sister Study (2008–2010), a sister-matched study of 1,419 cases diagnosed with breast cancer before the age of 50 years and 1,665 controls. We assessed exposures up to a family-specific index age to ensure comparable opportunities for exposures and used propensity scores to control for birth cohort effects on HT use. Ever HT use was uncommon (7% and 11% in cases and controls, respectively). Use of estrogen plus progestin was not associated with an increased risk of young-onset breast cancer (odds ratio = 0.80, 95% confidence interval: 0.41, 1.59). Unopposed estrogen use was inversely associated with the risk of young-onset breast cancer (odds ratio = 0.58, 95% confidence interval: 0.34, 0.99). Duration of use, age at first use, and recency of use did not modify these associations

Neighborhood-level and individual-level correlates of cannabis use among young persons living with HIV/AIDS

In addition to individual characteristics, there may be a wide range of environmental or neighborhood stressors that contribute to elevated cannabis use in groups of youth living with HIV/AIDS (YLHIV); however, the effects of social disorganization on cannabis use in YLHIV to date have not been studied

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD

Shiga-toxigenic Escherichia coli O157 in Agricultural Fair Livestock, United States

Organisms were common in ruminants, swine, and pest flies

Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor

Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors

Determination of quantitative trait loci (QTL) for early maturation in rainbow trout (Oncorhynchus mykiss)

To identify quantitative trait loci (QTL) influencing early maturation (EM) in rainbow trout (Oncorhynchus mykiss), a genome scan was performed using 100 microsatellite loci across 29 linkage groups. Six inter-strain paternal half-sib families using three inter-strain F(1) brothers (approximately 50 progeny in each family) derived from two strains that differ in the propensity for EM were used in the study. Alleles derived from both parental sources were observed to contribute to the expression of EM in the progeny of the brothers. Four genome-wide significant QTL regions (i.e., RT-8, -17, -24, and -30) were observed. EM QTL detected on RT-8 and -24 demonstrated significant and suggestive QTL effects in both male and female progeny. Furthermore, within both male and female full-sib groupings, QTL on RT-8 and -24 were detected in two or more of the five parents used. Significant genome-wide and several strong chromosome-wide QTL for EM localized to different regions in males and females, suggesting some sex-specific control. Namely, QTL detected on RT-13, -15, -21, and -30 were associated with EM only in females, and those on RT-3, -17, and -19 were associated with EM only in males. Within the QTL regions identified, a comparison of syntenic EST markers from the rainbow trout linkage map with the zebrafish (Danio rerio) genome identified several putative candidate genes that may influence EM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10126-008-9098-5) contains supplementary material, which is available to authorized users