Faculty Bibliography

BACKGROUND: Cutaneous leishmaniasis is a serious public health problem in the developing world. The main therapeutic agent--pentavalent antimony, developed >50 years ago--is expensive, often accompanied by severe adverse effects, and complicated by the emergence of drug resistance. Better therapies are urgently needed. In the present pilot study, we compared the use of imiquimod, an immunomodulatory molecule, to the use of meglumine antimoniate alone and in combination for the initial treatment of cutaneous leishmaniasis. MATERIALS AND METHODS: Patients with newly diagnosed cutaneous leishmaniasis were enrolled from a single referral center in Lima, Peru, from August 2005 through October 2005. Patients were randomly assigned to 1 of 3 treatment groups and received either imiquimod 7.5% cream administered topically every other day for 20 days, intravenous meglumine antimoniate administered at a dosage of 20 mg/kg per day every day for 20 days, or combination therapy with both intravenous meglumine antimoniate and imiquimod 7.5% cream. Patients were evaluated weekly and at 1 and 3 months after treatment. Patients who had healed lesions at 3 months were considered to be clinically cured. RESULTS: Although several patients showed initial resolution of symptoms with imiquimod treatment alone, all of these patients experienced relapse after treatment discontinuation. Four (57%) of 7 patients treated with meglumine antimoniate alone and 7 (100%) of 7 patients treated with combination therapy were cured. Combination therapy was not only more effective than the other 2 treatments (P<.05) but also led to faster healing and better cosmetic results. CONCLUSION: Combination therapy with imiquimod and meglumine antimoniate is a promising regimen for the initial treatment of cutaneous leishmaniasis that warrants additional larger studies.

The 1896 precore (PC) mutation is the most frequent cause of hepatitis B virus e-antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Detection of the 1896 PC mutation has application in studies monitoring antiviral therapy and the natural history of the disease. Identification of this mutation is usually performed by direct sequencing, which is both costly and laborious. The aim of this study was to develop a rapid, high-throughput assay to detect the 1896 PC mutation using real-time PCR and molecular-beacon technology. The assay was initially standardized on oligonucleotide targets and plasmids containing the wild-type (WT) and PC mutation and then tested on plasma samples from children with HBV DNA of >10(6) copies/ml. Nine individuals were HBeAg negative and suspected to harbor HBeAg mutations, while 12 children were HBeAg positive and selected as controls. Ninety percent (19 of 21) of plasma samples tested with molecular beacons were in complete agreement with sequencing results. The remaining 10% (2 of 21) of samples were identified as heterogeneous mixtures of WT and mutant virus by molecular beacons, though sequencing found only a homogeneous mutant in both cases. Overall, the 1896 PC mutation was detected by this assay in 55.5% of the children with HBeAg-negative infection. In summary, this assay is a rapid, sensitive, and specific technique that effectively discriminates WT from 1896 PC mutant HBV and may be useful in clinical and epidemiological studies

OBJECTIVES:: Three HIV/hepatitis C virus (HCV)-coinfected children and the mothers of 2 were studied to examine the nature of perinatal HCV infection in HIV-coinfected infants and to assess the evolution of viral quasispecies thereafter. Sequences of the hypervariable region in the N terminus of the E2/NS1 region (HVR-1) of the children and their mothers were compared. HCV quasispecies changes in the infants were tracked over several years. METHODS:: Sequence similarity comparisons and phylogenetic trees were derived from cDNA of plasma isolates. Quantitation of plasma HCV and HIV was performed in the children, as well as CD4 T-cell percentage and liver transaminases. RESULTS:: Phylogenetic analysis of the mother-child pairs suggested that transmission of multiple dominant and nondominant variants identified in the mother were seen. HCV diversification in the children was seen as early as 2 months of life. The child with the best immune status and HIV control demonstrated the most diversification throughout. CONCLUSION:: Multiples HCV variants transmitted from mother to child and their early changes in the child may be related to maternal antibody. Variation after the 1st year of life may reflect immunologic pressure from the child. There was no trend suggesting that the presence or absence of selective immunologic pressure affected HCV load or liver transaminase values

Despite the recent approval of lamivudine for the treatment of children with chronic hepatitis B virus (HBV) infection, there is insufficient information on the kinetics of HBV clearance and the factors that predict a favorable treatment response to lamivudine in this population. In a small retrospective study of 16 HBV-infected children treated with lamivudine, we examined changes in virus load and other factors associated with hepatitis B e antigen (HBeAg) clearance. High pretherapy alanine aminotransferase level, low serum HBV DNA load, and age at the start of treatment were independently associated with HBeAg clearance. HBeAg clearance was also associated with the achievement of specific levels of virus suppression, and failure to achieve those levels was associated with the development of lamivudine resistance. Additional studies are necessary to provide better indications and guidelines for the treatment of children with chronic HBV infection