Faculty Bibliography

HIV may induce gastrointestinal (GI) mucosal immune dysregulation similar to inflammation observed in ulcerative colitis (UC). Colorectal biopsies from healthy controls (N=12) and from participants with HIV (N=20) or UC (N=9) were subjected to real time (RT)-PCR for selected cytokines, chemokines, antimicrobial peptides, Toll-like receptors, and inflammatory signaling and epithelial barrier proteins. HIV long terminal repeat relative copy number (RCN) in HIV participant biopsies was quantified by RT-PCR. Mean interleukin (IL)-6 mRNA levels did not differ significantly between HIV and UC participants (p=0.48) but were significantly higher relative to control mRNA levels only for HIV participants (p=0.03). Mean IL-8 and human defensin (HD) 5 mRNA levels were similar between HIV and UC participants (p=1.0 and p=0.35, respectively) and were significantly greater in both groups relative to controls (p<0.05 for all). Human beta-defensin (HBD)-2 mRNA levels were higher in UC relative to HIV and control participants (p<0.01 for both). Conversely, HBD-1 mRNA levels were downregulated in UC vs. HIV participants (p=0.01). Mediator gene expression did not differ significantly between HIV participants with detectable (N=10) or nondetectable (N=10) plasma viral loads. Tissue HIV relative copy number (RCN) correlated with plasma viral load (r=0.88, p<0.01) but not with mediator mRNA levels. The results of this study indicate that both chronic HIV infection and UC are associated with similar patterns of IL-6, IL- 8, and HD5 expression in colorectal biopsy tissue. These findings suggest overlapping mechanisms for GI mucosal inflammation in these two illnesses and merit further investigation in larger studies.

BACKGROUND: Recent cases of donor-derived infections raise the question of how best to screen donors without excessive restriction of the donor pool. METHODS: The New York Organ Donor Network (NYODN) established an Infectious Diseases Working Group (IDWG) in 2008, which established an on-call schedule of voluntary transplant infectious disease physicians to provide remote evaluations for donors at increased risk for disease transmission. RESULTS: Data were reviewed from 40 available IDWG evaluations from 2008 to 2011. Eighteen cases (45%) were considered to be at unacceptable risk for infection transmission. Sixteen of these cases were excluded from donation secondary to IDWG recommendation; there was limited recipient center interest in the remaining two cases. Approximately 22 (55%) cases were categorized by the IDWG as acceptable, with 14 proceeding to recovery of 49 organs. IDWG physician recommendations were conveyed to recipient centers, and screening guidelines for donors were revised based on the IDWG experiences. CONCLUSION: Establishment of a donation service area disease transmission evaluation service is a valuable program for donor screening and may promote dissemination of more detailed donor information to recipient centers.

This manuscript reports the clinical, microbiological, and genetic characteristics of carbapenem-resistant K. pnuemoniae isolates from pediatric patients at a tertiary-care children's hospital. Although there is an extensive body of literature describing carbapenem-resistant Klebsiella infections in adults, pediatric data are comparatively limited.

The risk of male to female transmission of HIV is impacted by baseline inflammation in the female genital tract, semen viral load and seminal plasma's ability to induce specific patterns of cervical cytokine signalling and influx of immune cell populations. Disruption of the epithelial barrier during non-consensual intercourse may trigger further inflammation and initiation of cell-signalling pathways, thus facilitating transmission of HIV and expansion of local infection. Adolescent and pregnant women are at high risk for sexual violence and may exhibit alterations of genital mucosal immunity that promote immune activation, making them uniquely vulnerable to HIV acquisition.

BACKGROUND: Genital tract secretions provide variable inhibitory activity against herpes simplex virus (HSV) ex vivo. We hypothesize that the anti-HSV activity may prevent the spread of virus from the more commonly affected sites, such as the external genitalia, to the upper genital tract. METHODS: The antimicrobial activity of cervicovaginal lavage (CVL) and concentrations of mucosal immune mediators were measured in 10 HIV-seronegative women with an active external herpetic lesion and compared with 10 HIV-seronegative women who were HSV-1 and HSV-2 seronegative. Samples were obtained at the time of a symptomatic external lesion (day 0), after 1 week of oral acyclovir (day 7), and 1 week after completing treatment (day 14). Controls were evaluated at parallel intervals. RESULTS: The anti-HSV activity was higher in CVL obtained from cases compared to controls at presentation (day 0) (54.3% vs. 28%), fell to similar levels on day 7, and then rebounded on day 14 (69% vs. 25%). The anti-HSV activity correlated positively and significantly with the concentrations of several inflammatory proteins; the concentrations of these proteins tended to be higher in cases compared with controls and followed a similar temporal pattern. CONCLUSIONS: Increases in inflammatory immune mediators and anti-HSV activity were detected in CVL at the time of clinical outbreaks and after completion of a short course of acyclovir. These mucosal responses may protect against HSV spread but could facilitate HIV infection and contribute to the clinical observation that, independent of clinical lesions, HSV-2 is a risk factor for HIV acquisition.

Cryptococcosis during pregnancy is well documented, but transmission of infection to the fetus is rare. We describe a premature neonate born to a mother with congenitally acquired human immunodeficiency virus (HIV) and active cryptococcosis. Histological examination of the placenta revealed Cryptococcus neoformans within the maternal intervillous space with focal invasion into the chorionic villi. A positive serum cryptococcal antigen (1:2) was detected on days 1 and 5 of life. The neonate had no evidence of central nervous system disease and was treated with fluconazole with resolution of antigenemia. This case highlights both the potential for transplacental transmission of C. neoformans infection and the complexities of caring for pregnant mothers who themselves are congenitally infected with HIV.

CMI responses, combined with quantification of CMV DNA (DNAemia), may identify transplantation recipients at risk for invasive disease. PBMC were collected in pediatric transplantation candidates at one, three, and six months post-transplant in 10 subjects (six renal, three cardiac, one stem cell) and at single time points in eight HC and 14 children greater than one yr post-transplant (LTTx). Cells were stimulated with anti-CD3mAb or CMV pp65 peptide pools and responses assessed by IFNG enzyme-linked immunosorbent spot assay and cytokine secretion. IFNG responses to anti-CD3mAb were significantly lower pretransplant relative to HC and were further decreased at one and three months post-transplant, but recovered to levels comparable to HC by six months. Responses to pp65 among CMV-seropositive recipients followed a similar pattern but recovered by three months. CMV-seropositive LTTx and HC showed a Th1 cytokine response to pp65 stimulation. Three LTTx subjects developed CMV DNAemia; two demonstrated decreased responses to anti-CD3mAB (and pp65 in the CMV seropositive subject) at the onset of DNAemia, which recovered as DNAemia resolved. Monitoring CMI in children is feasible and may provide an adjunct biomarker to predict CMV progression and recovery.