Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease

BACKGROUND: Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. METHODS: We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS: We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. CONCLUSIONS: Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.     

Intrarectal administration of oxygenated perfluorodecalin promotes healing of murine colitis by targeting inflammatory hypoxia

Intestinal inflammation is associated with enhanced mucosal hypoxia, which contributes to the ongoing inflammatory process and hampers appropriate mucosal healing. We questioned whether local treatment with an oxygen (O(2))-carrying and -releasing molecule (oxygenated perfluorodecalin, O(2)-PFD) could positively influence the course of experimental colitis. The impact of intrarectal (IR) treatment with O(2)-PFD was tested using the murine dextran sodium sulfate (DSS)-induced model of distal colitis, both in preventive and therapeutic settings. Colonic mucosal hypoxia was visualized by pimonidazole staining. Colonic permeability was evaluated with FITC-dextran. In the preventive study, mice treated with O(2)-PFD were protected against DSS colitis compared with saline-treated mice, as demonstrated by reduced shortening of colon length, reduced colonic tumor necrosis factor-alpha levels and a lower histological inflammation score (P<0.05 for all parameters). In the therapeutic study, administration of O(2)-PFD resulted in accelerated recovery of colitis compared with saline-treated littermates, and this was reflected by a better weight evolution, lower myeloperoxidase activity and a lower histological inflammation score (P<0.05 for all parameters). It was found that O(2)-PFD established its therapeutic effects through (1) intrinsic anti-inflammatory effects of the PFD molecule and (2) O(2)-induced preservation and healing of the intestinal epithelial surface. Further in vitro and in vivo studies showed that the barrier-protective activity of O(2)-PFD was obtained through prevention of colonocyte apoptosis and stimulation of colonocyte proliferation during inflammatory hypoxia. These data show that IR treatment with O(2)-PFD promotes colitis healing by the combined actions of direct anti-inflammatory effects and O(2)-induced restitution of the epithelial barrier. As such, O(2)-PFD enemas could be an attractive treatment option for patients with distal inflammatory bowel disease.     

Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample*

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM‐III‐R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo‐affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2–5 cM for the region surrounding the α‐7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds‐only linkage analysis. In the European American families, there was a maximum Z‐score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA‐7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds. © 2001 Wiley‐Liss, Inc.