One Health Education for Future Physicians: A Case Report of Cat-Transmitted Sporotrichosis.

A healthy 35-year-old Brazilian woman presented with persistent redness, swelling, and multiple wounds on the hand 2 weeks after a cat bite in her home country. She was treated twice with amoxicillin-clavulanate but failed to demonstrate improvement. She then presented to our institution with a newly developed abscess on the right hand. Incision and drainage were performed and she was admitted to the hospital. She was subsequently treated with broad-spectrum antibiotics. Her symptoms improved but did not resolve. Four days after hospital discharge, a wound culture resulted as positive for Sporothrix schenchii. The patient was treated with itraconazole. Sporotrichosis is endemic in many countries including Brazil and is known to be transmitted by cat bites. Sporotrichosis should be considered in the differential diagnosis for patients who have symptoms of cellulitis after cat bites in an endemic area.

Frequencies of FoxP3+ naive T cells are related to both viral load and naive T cell proliferation responses in HIV disease.

HIV infection results in depletion and dysfunction of naïve CD4(+) T cells. The mechanisms underlying these deficiencies are not understood. We investigated the frequencies of CD4(+) naïve subsets in HIV disease as defined by expression of CD25 and/or FoxP3 and the relationship of these frequencies to naïve T cell proliferation function. We observed increased proportions of CD25(+)FoxP3(+) and CD25(+)FoxP3(-) cells and decreased proportions of CD25(-)FoxP3(-) cells within the naïve CD4(+) cell compartment from HIV-infected persons compared with findings in healthy donors. These perturbations were related to higher plasma HIV RNA levels but not with higher immune activation, as measured by the proportions of CD38(+) memory CD4(+) T cells. Naïve T cell proliferation responses to mitogen stimulation were inversely related to the frequencies and absolute numbers of FoxP3(+) naïve T cells. MDA, a marker of oxidative stress, and sCD14, a marker of monocyte activation and a surrogate for microbial translocation, were increased in serum samples from HIV(+) donors; however, neither marker was related to naïve T cell function in HIV(+) donors. These observations suggest that alterations in naïve T cell subset frequencies could contribute to naïve T cell dysfunction in HIV disease, but these alterations are not necessarily the result of chronic immune activation.

Safety, pharmacokinetics, and antiviral activity of HGS004, a novel fully human IgG4 monoclonal antibody against CCR5, in HIV-1-infected patients.

BACKGROUND: HGS004 is a fully human immunoglobulin (Ig) G4 monoclonal antibody against CC chemokine receptor 5 (CCR5) with robust in vitro activity against a diverse panel of CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. METHODS: A single-blind, randomized, placebo-controlled study was conducted in patients infected with CCR5-tropic HIV-1 to evaluate the safety, pharmacokinetics, and antiviral activity of HGS004. Sixty-three subjects were randomized into 5 dose cohorts (0.4, 2, 8, 20, and 40 mg/kg) and received a single intravenous dose of HGS004 or placebo. RESULTS: HGS004 was well tolerated, and no dose-limiting toxicities were observed. Pharmacokinetics were nonlinear across the 0.4-40-mg/kg dose range, with dose-proportional increases in maximum concentration, although the area under the curve increased more than proportionally to dose. High levels of receptor occupancy were observed for up to 28 days in the higher-dose cohorts. Plasma HIV-1 RNA reductions of >1 log(10) at day 14 were observed in 14 (54%) of 26 subjects in the 8-, 20-, and 40-mg/kg cohorts. In the 40-mg/kg cohort, 4 of 10 subjects had a >1 log(10) HIV-1 RNA reduction at day 28. Drug concentrations relative to isolate sensitivity (the ratio of the concentration at day 14 to IC(90)) predicted antiviral response on day 14. CONCLUSIONS: HGS004 is safe and well tolerated and demonstrates meaningful antiviral activity when administered to patients infected with CCR5-tropic HIV-1.

Update on the Management of Hepatitis C in Liver Transplant Recipients.

Hepatic failure due to hepatitis C is the leading indicator for orthotopic liver transplantation (OLT) in the United States. Unfortunately, recurrent hepatitis C virus infection is essentially universal following orthotopic liver transplantation. Although significant advances have been made in the past decade for the treatment of hepatitis C, a similar level of success has not yet been achieved for most hepatitis C virus-infected liver transplant recipients. In addition, deleterious side effects of the currently available antiviral agents continue to significantly hamper their use. Several recent reports, however, indicate that newer immunosuppressive regimens combined with novel modifications of existing treatment paradigms will likely lead to improved clinical outcomes for the hepatitis C virus-infected liver transplant recipient.