Wounds on wheels: implementing a specialized wound clinic within an established syringe exchange program in Baltimore, Maryland.

People who inject drugs (PWID) experience a high incidence of abscesses and chronic wounds. However, many PWID delay seeking care for their wounds. In 2012, the Baltimore Needle Exchange Program (BNEP) in Baltimore, Maryland, partnered with the Johns Hopkins Wound Healing Center to establish a mobile BNEP Wound Clinic. This clinic provided specialized wound care for BNEP patients. In sixteen months, the clinic treated 78 unique patients during 172 visits overall. On average, each visit cost the program $146.45, which was substantially less than clinic-based treatment. This program demonstrates that specialized wound care can be effectively provided through mobile outreach. A community-based service delivery approach might serve as a model for local health departments looking to improve the health of PWID.

Self-care and risk reduction habits in older injection drug users with chronic wounds: a cross-sectional study.

BACKGROUND: We surveyed a population of injection drug users (IDUs) frequenting the mobile Baltimore City Needle Exchange Program (BNEP) to investigate self-care factors associated with chronic wounds, a significant cause of morbidity especially among older IDUs. METHODS: Participants ≥18 years old completed a survey regarding chronic wounds (duration ≥8 weeks), injection and hygiene practices. Study staff visually verified the presence of wounds. Participants were categorized into four groups by age and wound status. Factors associated with the presence of chronic wounds in participants ≥45 years were analyzed using logistic regression. RESULTS: Of the 152 participants, 19.7% had a chronic wound. Of those with chronic wounds, 18 were ≥45 years old (60.0%). Individuals ≥45 years old with chronic wounds were more likely to be enrolled in a drug treatment program (Odds ratio (OR) 3.4, 95% Confidence interval (CI) 1.0-10.8) and less likely to use cigarette filters when drawing up prepared drug (OR 0.2, 95% CI 0.03-0.7) compared to the same age group without chronic wounds. Compared to individuals <45 years old without chronic wounds, individuals ≥45 with a chronic wound were more likely to report cleaning reused needles with bleach (OR 10.7, 95% CI 1.2-93.9) and to use the clinic, rather than an emergency room, as a primary source of medical care (OR 3.4, 95% CI 1.1-10.4). CONCLUSIONS: Older IDUs with chronic wounds have different, and perhaps less risky, injection and hygiene behaviors than their peers and younger IDUs without wounds in Baltimore City. Because of these differences, older IDUs with wounds may be more receptive to community-based healthcare and substance abuse treatment messages.

Effects of HIV-1 and herpes simplex virus type 2 infection on lymphocyte and dendritic cell density in adult foreskins from Rakai, Uganda.

BACKGROUND: Male circumcision reduces human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2) acquisition, and HSV-2 infection is associated with an increased risk of HIV acquisition. To assess the cellular basis for these associations, we estimated immunologic cellular densities in foreskin tissue. METHODS: Immunostained CD1a(+) dendritic cell and CD4(+) and CD8(+) T cell densities were quantified in foreskin samples obtained from medical circumcision in Rakai, Uganda (35 HIV-infected, HSV-2-infected men; 5 HIV-infected, HSV-2-uninfected men; 22 HIV-uninfected, HSV-2-infected men; and 29 HIV-uninfected, HSV-2-uninfected men. RESULTS: CD1A(+) dendritic cell densities did not vary by HIV or HSV-2 status. Compared with densities in HIV-uninfected, HSV-2-uninfected men (mean, 26.8 cells/mm(2)), CD4(+) T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm(2)), were significantly decreased in the HIV-infected, HSV-2-uninfected group (mean, 11.2; P < .05), and were increased in the HIV-uninfected, HSV-2-infected group (mean, 68.7; P < .05). Dermal CD8(+) T cell densities were higher in the HIV and HSV-2-coinfected group (mean, 102.9) than in the HIV-uninfected, HSV-2-uninfected group (mean, 10.0; P < .001), the HIV-infected, HSV-2-uninfected group (mean, 27.3; P < .001), and the HIV-uninfected, HSV-2-infected group (mean, 25.3; P < .005). DISCUSSION: The increased CD4(+) cellular density in the HIV-uninfected, HSV-2-infected men may help to explain why HSV-2-infected men are at increased risk of HIV acquisition. The absence of this increase in men coinfected with both HIV and HSV-2 is likely in part the result of the progressive loss of CD4(+) cells in HIV infection. Conversely, HIV and HSV-2 coinfection appears to synergistically increase CD8(+) T cell densities.

An atypical case of fatal zygomycosis: simultaneous cutaneous and laryngeal infection in a patient with a non-neutropenic solid prostatic tumor.

We describe what we believe is the first reported case of simultaneous highly invasive cutaneous and laryngopharyngeal zygomycosis in a non-neutropenic, nondiabetic but immunosuppressed patient with prostate cancer. An invasive fungal process was not suspected until late in the patient's hospital course; when it was, a tracheotomy and direct laryngoscopic biopsies were performed. Unresectable invasive zygomycosis with Rhizopus rhizopodiformis was diagnosed. The patient was managed with liposomal amphotericin B initially and later with palliative medical therapy until he died. This case emphasizes the need for a rapid and specific diagnosis with timely introduction of appropriate antifungal management, particularly now that voriconazole is frequently used as empiric prophylaxis against aspergillosis in high-risk patients.

Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis.

BACKGROUND: Observational studies suggest that maternal human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection is associated with increased odds of vertical HCV transmission. We performed a meta-analysis to summarize current evidence. METHODS: We systematically searched for relevant articles published during the period from January 1992 through July 2006 and independently abstracted articles that met our inclusion criteria. Under a random effects model, we calculated the pooled odds ratio for vertical HCV transmission according to maternal HIV-HCV coinfection status and performed sensitivity analyses. RESULTS: Ten articles met our inclusion criteria. Study quality varied widely, and study estimates displayed high statistical heterogeneity. Restriction of the analysis to studies that included >50 HIV-HCV-coinfected women provided our most reliable estimate: maternal HIV-HCV coinfection increases the odds of vertical HCV transmission by approximately 90% (odds ratio, 1.9; 95% confidence interval, 1.36-2.67), compared with maternal HCV infection alone. When we restricted analyses to HIV-infected mothers with HCV viremia, the odds of vertical HCV transmission were 2.82-fold (95% confidence interval, 1.17-fold to 6.81-fold) greater than the odds for HIV-infected mothers without HCV viremia. CONCLUSIONS: HIV-HCV-coinfected women have significantly higher odds of transmitting HCV to their infants than do women who are infected with HCV alone.

The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli.

In 1982, hemorrhagic colitis and hemolytic-uremic syndrome were linked to infection with Escherichia coli O157:H7, a serotype now classified as Shiga toxin-producing E. coli (STEC). Thereafter, hemorrhagic colitis and hemolytic-uremic syndrome associated with non-O157 STEC serogroups were reported, with the frequency of non-O157 STEC illness rivaling that of O157:H7 in certain geographic regions. In the United States, non-O157 E. coli may account for up to 20%-50% of all STEC infections. A high index of suspicion, paired with options to test for non-O157 STEC infection, are necessary for early recognition and appropriate treatment of these infections. Supportive care without the use of antibiotics is currently considered to be optimal treatment for all STEC infections. This commentary provides a perspective on the non-O157 STEC as human pathogens, how and when the clinician should approach the diagnosis of these organisms, and the challenges ahead.

High rates of abscesses and chronic wounds in community-recruited injection drug users and associated risk factors.

OBJECTIVES: Abscesses and chronic wounds are common among injection drug users (IDUs) though chronic wounds have been understudied. We assessed the risk factors associated with both acute and chronic wounds within a community-based population of IDUs frequenting the Baltimore City Needle Exchange Program (BNEP). METHODS: We performed a cross-sectional study of BNEP clients aged 18 years or more who completed an in-person survey regarding active or prior wounds including abscesses (duration <8 weeks) and chronic wounds (duration ≥8 weeks), injection practices, and skin care. Factors associated with wounds were analyzed using univariate and multivariate logistic regressions. RESULTS: Of the 152 participants, 63.2% were men, 49.3% were white, 44.7% were African American, 34.9% had any type of current wound, 17.8% had an active abscess, and 19.7% had a current chronic wound. Abscesses were more common in women (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.10-5.97) and those reporting skin-popping (OR, 5.38; 95% CI, 1.85-15.67). In a multivariate model, risk factors for an abscess included injecting with a family member/partner (adjusted OR [AOR], 4.06; 95% CI, 0.99-16.58). In a multivariable analysis of current chronic wounds, cleaning skin with alcohol before injection was protective (AOR, 0.061; 95% CI, 0.0064-0.58). CONCLUSIONS: Abscesses and chronic wounds were prevalent among a sample of IDUs in Baltimore. Abscesses were associated with injection practices, and chronic wounds seemed linked to varying skin and tool cleaning practices. There is a pressing need for wound-related education and treatment efforts among IDUs who are at greatest risk for skin-related morbidity.

Monocytes loaded with indocyanine green as active homing contrast agents permit optical differentiation of infectious and non-infectious inflammation.

Distinguishing cutaneous infection from sterile inflammation is a diagnostic challenge and currently relies upon subjective interpretation of clinical parameters, microbiological data, and nonspecific imaging. Assessing characteristic variations in leukocytic infiltration may provide more specific information. In this study, we demonstrate that homing of systemically administered monocytes tagged using indocyanine green (ICG), an FDA-approved near infrared dye, may be assessed non-invasively using clinically-applicable laser angiography systems to investigate cutaneous inflammatory processes. RAW 264.7 mouse monocytes co-incubated with ICG fluoresce brightly in the near infrared range. In vitro, the loaded cells retained the ability to chemotax toward monocyte chemotactic protein-1. Following intravascular injection of loaded cells into BALB/c mice with induced sterile inflammation (Complete Freund's Adjuvant inoculation) or infection (Group A Streptococcus inoculation) of the hind limb, non-invasive whole animal imaging revealed local fluorescence at the inoculation site. There was significantly higher fluorescence of the inoculation site in the infection model than in the inflammation model as early as 2 hours after injection (p<0.05). Microscopic examination of bacterial inoculation site tissue revealed points of near infrared fluorescence, suggesting the presence of ICG-loaded cells. Development of a non-invasive technique to rapidly image inflammatory states without radiation may lead to new tools to distinguish infectious conditions from sterile inflammatory conditions at the bedside.

The effects of circumcision on the penis microbiome.

BACKGROUND: Circumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significant decrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families we identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. CONCLUSIONS/SIGNIFICANCE: The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

Foreskin inflammation is associated with HIV and herpes simplex virus type-2 infections in Rakai, Uganda.

DESIGN: We assessed foreskin inflammation associated with HIV and herpes simplex virus type 2 (HSV-2) in circumcised men. METHODS: Foreskin tissues were assessed in 97 HIV-infected and 135 HIV-uninfected men enrolled in randomized trials of circumcision in Rakai, Uganda. Inflammation was quantified using an ordinal score evaluating extent, intensity, and cellular composition of infiltrates in the epithelium and stroma. Prevalence rate ratios of inflammation were estimated by multivariate Poisson regression. RESULTS: Foreskin inflammation was primarily focal. Epithelial inflammation was present in 4.2% of men with neither HIV nor HSV-2 infection; 7.8% of men with only HSV-2; 19.0% with HIV alone (P = 0.04); and 31.6% in HIV/HSV-2 coinfected men [prevalence rate ratio (PRR) 7.5, 95% confidence interval (CI) 2.3-23.8, P < 0.001]. Stromal inflammation was present in 14.1% of HIV/HSV-2 uninfected men, compared with 29.7% in men with HSV-2 alone (P = 0.03), 33.3% in men with HIV alone (P = 0.04), and 61.0% in men with HIV/HSV-2 coinfection (PRR 4.3, 95% CI 2.3-7.9, P < 0.001). In HIV-infected men, epithelial inflammation was associated with higher HIV viral load. Epithelial inflammation was more frequent among men reporting recent genital ulceration. Both epithelial and stromal inflammation were more common among men with smegma on physical examination. CONCLUSION: Foreskin inflammation is increased with HIV and HSV-2 infections, higher HIV viral load and presence of smegma. Foreskin inflammation may have implications for HIV transmission and acquisition in uncircumcised men.

Update on male circumcision: prevention success and challenges ahead.

This article reviews the findings of three trials of male circumcision for HIV prevention, with emphasis on the public health impact, cultural and safety concerns, implications for women, and the challenges of roll out. Three randomized trials in Africa demonstrated that adult male circumcision reduces HIV acquisition by 50% to 60%. As circumcision provides only partial protection, higher risk behaviors could nullify circumcision's effect. Additionally, circumcision among HIV-infected men does not directly reduce male-to-female HIV transmission among discordant couples, according to the results of a recent Ugandan study. The roll-out or full-scale implementation requires committed expansion into existing HIV prevention programs. Efforts should include attention to safety, implications for women, and risk compensation. Rapid, careful establishment of circumcision services is essential to optimize HIV prevention in countries with the highest prevalence.

Functional expression and characterization of macaque C-C chemokine receptor 3 (CCR3) and generation of potent antagonistic anti-macaque CCR3 monoclonal antibodies.

Eosinophils are major effector cells implicated in a number of chronic inflammatory diseases in humans, particularly bronchial asthma and allergic rhinitis. The beta-chemokine receptor C-C chemokine receptor 3 (CCR3) provides a mechanism for the selective recruitment of eosinophils into tissue and thus has recently become an attractive biological target for therapeutic intervention. In order to develop in vivo models of inflammatory diseases, it is essential to identify and characterize the homologues of human eotaxin (C-C chemokine ligand 11) and CCR3 from other species, such as non-human primates. Accordingly, we cloned the macaque eotaxin and CCR3 genes and revealed that they were 91 and 92% identical at the amino acid level to their human homologues, respectively. Macaque CCR3 expressed in the murine pre-B L1-2 cell line bound macaque eotaxin with high affinity (K(d) = 0.1 nm) and exhibited a robust eotaxin-induced Ca(2+) flux and chemotaxis. Characterization of beta-chemokines on native macaque CCR3 on eosinophils was performed by means of eotaxin-induced shape change in whole blood using a novel signaling assay known as gated autofluorescence forward scatter. Additionally, mAbs were raised against macaque CCR3 using two different immunogens: a 30-amino acid synthetic peptide derived from the predicted NH(2) terminus of macaque CCR3 and intact macaque CCR3-transfected cells. These anti-macaque CCR3 monoclonal antibodies exhibited potent antagonist activity in receptor binding and functional assays. The characterization of the macaque eotaxin/CCR3 axis and development of antagonistic anti-macaque CCR3 monoclonal antibodies will facilitate the development of CCR3 small molecule antagonists with the hope of ameliorating chronic inflammatory diseases in humans.