IFITM3 and susceptibility to respiratory viral infections in the community.

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.

Meningoencephalitis with Streptococcus equi Subspecies equi Leading to a Dural Arteriovenous Fistula.

Invasive infection with Lancefield group C streptococci in humans is extremely rare, with the vast majority of clinical isolates belonging to Streptococcus dysgalactiae subsp. equisimilis. We report a case of meningoencephalitis in a 69-year-old man caused by Streptococcus equi subsp. equi, a microbe that causes strangles in Equus caballus (i.e., the horse). This is only the fourth infection with this subtype of the central nervous system (CNS) reported in humans. The invasiveness of these bacteria, known to be capable of releasing strongly immunogenic exotoxins, is illustrated by white matter lesions that are present in the acute phase. This patient initially recovered well after treatment with antibiotics and glucocorticoids. However, the patient was readmitted 5 months later with multiple intraparenchymatous cerebral haemorrhages. Cerebral angiography confirmed the presence of a suspected superficial dural arteriovenous fistula (DAVF), which is seldom reported after CNS infection. The invasiveness of these bacteria was illustrated by white matter lesions present in the acute phase and the occurrence of a de novo dural arteriovenous fistula in the follow-up period.

Chlamydia pneumoniae-based atherosclerosis: a smoking gun.

Chronic and acute infectious diseases have been implicated in modifying the risk of atherosclerosis independently or in collaboration with conventional risk factors. During the past two decades, the discussion on microbial agents and atherosclerosis has mainly been centred on Chlamydia pneumoniae. The strongest evidence linking Chlamydia pneumoniae and atherosclerotic disease comes from in vitro experimental studies. In this review, we summarize and critically evaluate the available data of human diagnostic and therapeutic studies on the association of Chlamydia pneumoniae with atherosclerosis. Taking into account the human in vivo data, there is currently insufficient proof linking Chlamydia pneumoniae to atherosclerosis. At present, there are no indications for antibiotic treatment targeted at Chlamydia pneumoniae in the management of atherosclerosis.

Increased levels of tumor necrosis factor-alpha and decreased levels of interleukin-12 p 70 in tracheal aspirates, within 2 hrs after birth, are associated with mortality among ventilated preterm infants.

OBJECTIVE: To determine the association of antibacterial interleukin (IL)-12 p 70 levels as well as the pathogen-induced proinflammatory cytokine response in tracheal aspirate (TA) to respiratory failure and mortality among ventilated preterm infants. DESIGN: A prospective observational clinical cohort study with measurements of cytokine levels and microbial cultures of TA from ventilated preterm neonates. Interleukin (IL)-1 beta, IL-8, IL-6, IL-10, IL-12 p 70, and tumor necrosis factor (TNF)-alpha were measured in TA within 2 hrs of birth, and comorbidity characteristics were recorded prospectively. The association between cytokine levels in TA and neonatal mortality was determined, with correction for comorbidity factors by means of multivariate stepwise logistic regression. SETTING: A single tertiary neonatal intensive care unit at the University Hospital of Antwerp, Belgium. PATIENTS: One hundred forty-one neonates born before a gestational age of 31 wks and who required ventilation were enrolled in the study; 31 (22%) died and 37 (26%) had airway colonization. MEASUREMENTS AND MAIN RESULTS: The airway colonization rate was significantly greater among deceased neonates (45% vs. 21%; chi-square, 7.4; p=.007). Neonates who died had a significantly lower IL-12 p 70 cytokine level (6 pg/mL vs. 11 pg/mL; p<.05) in their TA. Neonates with a low IL-12 p 70 cytokine level had more pronounced respiratory failure (significantly higher oxygenation index, higher degree of radiologic respiratory distress syndrome, higher critical index for babies score, and more surfactant use). Multivariate analysis revealed that, after correction for severity of disease by critical index for babies score, the degree of intraventricular hemorrhage (odds ratio, 5.0 [95% confidence interval, 2.6-9.7]), low IL-12 p 70 levels (odds ratio, 4.9 [95% confidence interval, 2.1-11.7]), and high TNF-alpha levels in TA (odds ratio, 3.5 [95% confidence interval, 1.6-7.5]) were significantly associated with neonatal mortality. CONCLUSIONS: Pathogen-induced excessive production of the proinflammatory cytokine TNF-alpha and lack of antibacterial IL-12 p 70 response in the TA are associated with increased neonatal mortality among ventilated preterm infants.

Autoimmune gastropathy in type 1 diabetic patients with parietal cell antibodies: histological and clinical findings.

OBJECTIVE: Approximately 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients. RESEARCH DESIGN AND METHODS: Gastric biopsies from 88 consecutively recruited type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 +/- 13 years) were evaluated using the updated Sydney system. Immunostaining was done for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence, H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath test, and histology. Pentagastrin tests were performed in 42 subjects. RESULTS: Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P < 0.0001). PCA positivity (beta = 1.44; P = 0.04) and hypergastrinemia (beta = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015), pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P = 0.0002) were more frequent in AG+ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG+ patients, including 1 with linitis plastica. CONCLUSIONS: PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.

Time to positivity of neonatal blood cultures: fast and furious?

The aim of this study was to determine the time to positivity (TTP) of neonatal blood cultures, to investigate differences between early onset versus late-onset sepsis, and non-proven versus proven sepsis, and to examine differences in TTP by organism type using a retrospective observational study at the Neonatal Intensive Care Unit, Antwerp University Hospital, Belgium. The subjects were 1828 neonates with suspected sepsis who were treated with antimicrobials for at least 3 days. The TTP was recorded for all episodes of suspected sepsis in an approximately 6.5 year period. A total of 2916 blood cultures were collected, of which 437 (15%) became positive. The overall TTP was 21.33 h (Q1-Q3 13.17-32.46). The difference between the median TTP in early onset versus late-onset sepsis was 0.83 h (22.00 versus 21.17 h, P=0.75). The median TTP for Gram-negative organisms was 11.17 h (Q1-Q3 8.84-15.67), whereas the median TTP for Gram-positive organisms was 23.59 h (Q1-Q3 15.29-34.58, P<0.001). In Gram-positive isolates, the median TTP for coagulase-negative staphylococci (CNS) was 26.67 h (Q1-Q3 19.00-38.17), whereas the median TTP for non-CNS was 12.83 h (Q1-Q3 10.50-18.17, P<0.001). The median TTP in proven sepsis was 20.17 h (Q1-Q3 13.00-30.37), whereas it was 29.67 h (Q1-Q3 21.17-50.63, P<0.001) in non-proven sepsis. TTP of neonatal blood cultures was significantly shorter for Gram-negative organisms. We suggest shortening the total incubation time of neonatal blood cultures to a maximum of 3 days. However, blood cultures collected in infants<72 h of age might require a longer incubation time. According to our results, it may be safe to narrow the antimicrobial spectrum to solely target Gram-positive bacteria when the culture is still negative after 48 h, and to cease antimicrobial therapy when the culture is still negative after 72 h in clinically well infants.

Implications of antibodies to heat-shock proteins in ischemic heart disease.

OBJECTIVE: Experimental studies illustrate that priming with infectious agents, like Chlamydia pneumoniae, is involved in plaque formation and progression based on molecular mimicry with host heat-shock proteins (HSP). We have here evaluated the hypothesis that C. pneumoniae contributes to atherosclerotic disease progression via anti-HSP antibodies. METHODS: The blood circulation of 151 consecutive patients with ischemic heart disease was screened for antibodies against human and Chlamydia HSP60 and C. pneumoniae IgG. Antibody levels were associated with the angiographic extent of coronary atherosclerosis, with clinical symptoms of ischemic heart disease and with biochemical and functional endothelial dysfunction markers. RESULTS: Positive serology to human (11%) or Chlamydia HSP60 (22%) was not associated with the presence and extent of atherosclerosis, neither was it related with endothelial dysfunction. Patients with acute myocardial infarction had significantly lower Chlamydia HSP60 antibody levels (median OD 0.12, range: 0.02-0.75) than patients with stable (median OD 0.22, range: 0.02-2.67) or unstable angina pectoris (median OD 0.24, range: 0-2.48) (p=0.032). Subjects with positive C. pneumoniae IgG serology (if measured at a titre of 1:128) showed reduced flow-mediated vasodilation (p=0.024), but vasodilation responses did not differ in single-, two- or three-vessel disease. CONCLUSION: Overall, antibody responses to C. pneumoniae IgG, human or Chlamydia HSP60 are not associated with endothelial dysfunction and presence and severity of coronary artery disease, arguing against the suggestion that infection contributes to disease progression and supplying additional proof that C. pneumoniae is an unlikely major risk factor of coronary atherosclerosis.

Immunohistostaining assays for detection of Chlamydia pneumoniae in atherosclerotic arteries indicate cross-reactions with nonchlamydial plaque constituents.

Detection of Chlamydia pneumoniae antigens in PCR-negative atheromata by immunohistochemistry assays has given rise to controversies regarding a link between the bacterium and atherosclerosis. One hundred ninety-seven human arterial segments removed surgically were examined for C. pneumoniae DNA by conventional PCR with three different primer pairs and by real-time PCR in two different laboratories. No C. pneumoniae DNA was detected. Eighty atherosclerotic lesions were studied by immunohistochemistry assays. Immunoreactivity for C. pneumoniae was frequently present but was not related to the extent of atherosclerosis. Mammary arteries showed immunoreactivity. Serial sections of 17 atheromata were analyzed by Western blotting, histological staining, and UV fluorescence microscopy. Chlamydial proteins were not detected. The sites with positive results by C. pneumoniae immunohistostaining assays precisely matched the sites with autofluorescent ceroid deposits. Immunoblotting and antigenic staining for C. pneumoniae were negative in tests with fetal aortas. The absence of C. pneumoniae DNA in human atherosclerotic lesions, together with negative results for C. pneumoniae proteins by Western blotting analysis, and the perfect matching of C. pneumoniae immunoreactive sites with sites with autofluorescent ceroid deposits suggest a nonspecific reactivity of antichlamydial antibodies with plaque constituents. On the basis of the results of the present study, there are no arguments for an etiologic role of C. pneumoniae in atherosclerosis.