RESUMO
We report an uncommon case of a cutaneous infection with Mycobacterium fortuitum arising in a new tattoo. A 29-year-old man presented with a several month history of a non-pruritic papular eruption within a tattoo; the papules developed 1-to-2 weeks after the tattoo procedure. He denied similar symptoms with previous tattoos. He had been treated unsuccessfully with cephalexin. Histopathologic examination revealed perifollicular chronic and granulomatous inflammation, consistent with chronic folliculitis. Acid-fast bacilli culture identified Mycobacterium fortuitum complex. The patient was treated with a 2-month course of oral trimethoprim-sulfamethoxazole (160mg/800mg twice daily) and ciprofloxacin (250 mg twice daily), with clinical improvement at follow up after three weeks of the antibiotic regimen. Rapidly growing mycobacteria have emerged as a cause of tattoo-associated cutaneous infection in recent years. Diagnosis and treatment can be difficult without clinical suspicion. M. fortuitum and other rapidly growing mycobacteria should be considered in the differential diagnosis of tattoo-associated dermatologic complications.
Assuntos
Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/patologia , Mycobacterium fortuitum/isolamento & purificação , Tatuagem/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Cefalexina/uso terapêutico , Ciprofloxacina/uso terapêutico , Claritromicina/uso terapêutico , Técnicas Cosméticas , Quimioterapia Combinada , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
BACKGROUND: Reported infection rates for Mohs micrographic surgery (MMS) range from less than 1% to 3.5%. OBJECTIVE: To determine whether lower infection rates are possible for MMS with a consistently applied infection-control regimen. METHODS: A series of 832 consecutive patients with 950 tumors undergoing MMS formed the cohort for a retrospective study of infections before and after a program of heightened infection-control practices at a single-surgeon academic Mohs practice. The sterility upgrade included jewelry restrictions, alcohol hand scrub before stages and reconstruction, sterile gloves and (during reconstruction) sterile gowns for staff, and sterile towels and dressings for patients during Mohs stages. RESULTS: Infection rate was 2.5% (9 infections/365 tumors) before the sterility upgrade and 0.9% (5 infections/585 tumors) after, a statistically significant difference (p=.04). CONCLUSION: MMS already has low rates of infection, but this study shows that rigorous infection-control practices can significantly affect infection rates. The authors have indicated no significant interest with commercial supporters.
Assuntos
Controle de Infecções/métodos , Controle de Infecções/estatística & dados numéricos , Cirurgia de Mohs/estatística & dados numéricos , Neoplasias/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Antibioticoprofilaxia/estatística & dados numéricos , Estudos de Coortes , Feminino , Custos de Cuidados de Saúde , Humanos , Incidência , Controle de Infecções/economia , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs/efeitos adversos , Neoplasias/classificação , Estudos Retrospectivos , Medição de Risco , Esterilização/métodos , Esterilização/estatística & dados numéricos , Infecção da Ferida Cirúrgica/etiologia , Estados Unidos/epidemiologiaAssuntos
Granuloma Anular/complicações , Linfoma de Células B/patologia , Linfoma de Células T/complicações , Linfoma de Células T/patologia , Segunda Neoplasia Primária/complicações , Segunda Neoplasia Primária/patologia , Idoso , Cotovelo/patologia , Infecções por Vírus Epstein-Barr/complicações , Feminino , Citometria de Fluxo , Antebraço/patologia , Granuloma Anular/patologia , Humanos , Imuno-Histoquímica , Linfoma de Células B/virologiaRESUMO
BACKGROUND: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. METHODS: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays. RESULTS: The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in approximately 20% of individuals. CONCLUSIONS: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.
Assuntos
Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Vacinas de DNA , Vacinas Virais , Adolescente , Adulto , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Testes de Neutralização , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/imunologia , Glicoproteína da Espícula de Coronavírus , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/imunologia , Adulto JovemRESUMO
West Nile virions incorporate 180 envelope (E) proteins that orchestrate the process of virus entry and are the primary target of neutralizing antibodies. The E proteins of newly synthesized West Nile virus (WNV) are organized into trimeric spikes composed of pre-membrane (prM) and E protein heterodimers. During egress, immature virions undergo a protease-mediated cleavage of prM that results in a reorganization of E protein into the pseudo-icosahedral arrangement characteristic of mature virions. While cleavage of prM is a required step in the virus life cycle, complete maturation is not required for infectivity and infectious virions may be heterogeneous with respect to the extent of prM cleavage. In this study, we demonstrate that virion maturation impacts the sensitivity of WNV to antibody-mediated neutralization. Complete maturation results in a significant reduction in sensitivity to neutralization by antibodies specific for poorly accessible epitopes that comprise a major component of the human antibody response following WNV infection or vaccination. This reduction in neutralization sensitivity reflects a decrease in the accessibility of epitopes on virions to levels that fall below a threshold required for neutralization. Thus, in addition to a role in facilitating viral entry, changes in E protein arrangement associated with maturation modulate neutralization sensitivity and introduce an additional layer of complexity into humoral immunity against WNV.
Assuntos
Anticorpos Antivirais/imunologia , Proteínas do Envelope Viral/imunologia , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologia , Animais , Anticorpos Antivirais/metabolismo , Linhagem Celular , Chlorocebus aethiops , Ensaios Clínicos Fase I como Assunto , Relação Dose-Resposta Imunológica , Humanos , Testes de Neutralização , Ligação Proteica , Biossíntese de Proteínas , Células Vero , Proteínas do Envelope Viral/metabolismo , Vírion/imunologia , Vírion/metabolismo , Vírus do Nilo Ocidental/crescimento & desenvolvimentoRESUMO
Needle-free delivery of a six-plasmid HIV-1 DNA vaccine encoding EnvA, EnvB, EnvC, and subtype B Gag, Pol, and Nef underwent open-label evaluation in 15 subjects; 14 completed the 0, 1, 2 month vaccination schedule. T cell responses to HIV-specific peptide pools were detected by intracellular cytokine staining of CD4(+) [13/14 (93%)] and CD8(+) [5/14 (36%)], and by ELISpot in 11/14 (79%). Ten of 14 (71%) had ELISA antibody responses to Env proteins. Compared to a four-plasmid product, Gag- and Nef-specific T cell responses were improved, while Env-specific responses were maintained. This candidate vaccine has now advanced to Phase II evaluation.
Assuntos
Vacinas contra a AIDS/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Vacinas de DNA/administração & dosagem , Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Adolescente , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , Produtos do Gene nef/imunologia , Anticorpos Anti-HIV/biossíntese , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Imunidade Celular/imunologia , Masculino , Plasmídeos/genética , Plasmídeos/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia , Vacinas de DNA/efeitos adversos , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência HumanaRESUMO
BACKGROUND: The development of an effective human immunodeficiency virus (HIV) vaccine is a high global priority. Here, we report the safety, tolerability, and immunogenicity of a replication-defective recombinant adenovirus serotype 5 (rAd5) vector HIV-1 candidate vaccine. METHODS: The vaccine is a mixture of 4 rAd5 vectors that express HIV-1 subtype B Gag-Pol fusion protein and envelope (Env) from subtypes A, B, and C. Healthy, uninfected adults were randomized to receive 1 intramuscular injection of placebo (n=6) or vaccine at dose levels of 10(9) (n=10), 10(10) (n=10), or 10(11) (n=10) particle units and were followed for 24 weeks to assess immunogenicity and safety. RESULTS: The vaccine was well tolerated but was associated with more reactogenicity at the highest dose. At week 4, vaccine antigen-specific T cell responses were detected in 28 (93.3%) and 18 (60%) of 30 vaccine recipients for CD4(+) and CD8(+) T cells, respectively, by intracellular cytokine staining assay and in 22 (73%) of 30 vaccine recipients by enzyme-linked immunospot assay. Env-specific antibody responses were detected in 15 (50%) of 30 vaccine recipients by enzyme-linked immunosorbant assay and in 28 (93.3%) of 30 vaccine recipients by immunoprecipitation followed by Western blotting. No neutralizing antibody was detected. CONCLUSIONS: A single injection induced HIV-1 antigen-specific CD4(+) T cell, CD8(+) T cell, and antibody responses in the majority of vaccine recipients. This multiclade rAd5 HIV-1 vaccine is now being evaluated in combination with a multiclade HIV-1 DNA plasmid vaccine.
Assuntos
Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/imunologia , Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Náusea/etiologia , Vacinação , Vacinas contra a AIDS/administração & dosagem , Adenovírus Humanos/genética , Adolescente , Adulto , Especificidade de Anticorpos , Western Blotting , Citocinas/análise , Citocinas/biossíntese , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Proteínas de Fusão gag-pol/imunologia , Produtos do Gene env/imunologia , Vetores Genéticos , Humanos , Injeções Intramusculares , Masculino , Recombinação Genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Produtos do Gene env do Vírus da Imunodeficiência HumanaRESUMO
BACKGROUND: Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. METHODS: VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. RESULTS: The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon- gamma -producing T cells and an increased frequency of interleukin-2-producing T cells at 1 year. CONCLUSIONS: DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.
Assuntos
Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/imunologia , Vetores Genéticos , Infecções por HIV/imunologia , HIV-1/imunologia , Esquemas de Imunização , Testes de Neutralização , Plasmídeos , Vacinação , Vacinas contra a AIDS/administração & dosagem , Adolescente , Adulto , Anticorpos Antivirais/sangue , Especificidade de Anticorpos , Western Blotting , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/análise , Citocinas/biossíntese , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Fusão gag-pol/genética , Proteínas de Fusão gag-pol/imunologia , Produtos do Gene nef/genética , Produtos do Gene nef/imunologia , Infecções por HIV/sangue , Humanos , Injeções Intramusculares , Masculino , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência HumanaRESUMO
Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4(+) T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8(+) T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.
Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Vacinas de DNA/imunologia , Adolescente , Adulto , Anticorpos Antivirais/biossíntese , Relação Dose-Resposta Imunológica , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/efeitos adversos , Feminino , Doença pelo Vírus Ebola/imunologia , Humanos , Injeções Intramusculares , Masculino , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversosRESUMO
Elevated mortality rates of lung cancer in the Mississippi River corridor in Louisiana have been clearly documented for the past half-century and rank among the highest in the nation. A population-based case-control study of lung cancer termed Lower Mississippi River Interagency Cancer Study was conducted in southern Louisiana. Lung tumor specimens were collected, isolated by laser capture microdissection, subjected to PCR to amplify KRAS, and sequenced to confirm mutation status and specificity. Of the 116 lung tumors analyzed to date, 32 (27.6%) contained mutations in either codon 12 or 13 of KRAS. This frequency is comparable to that reported in the literature; however, the mutation spectrum was strikingly different. Of the 32 mutations observed, 21 (65.6%) resulted in the inappropriate insertion of cysteine, 6 (18.8%) resulted in the insertion of serine, 3 (9.4%) resulted in the insertion of valine, and 1 (3.1%) each resulted in the insertion of aspartate and alanine. These data indicate that an abnormally high proportion of cysteine (P = 0.010) and serine (P = 0.002) mutations was observed in our sample group versus lung cancers reported in the literature. KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373). No association was found between the observed mutation spectrum and known lung cancer risk factors.