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Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm(3). Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. clinicaltrialsregister.eu _2007-002359-18IT.

Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

In this article, based on Appreciative Inquiry, we present and discuss the best practices of a group of preceptors from a multiprofessional health residency program in Brazil. The best practices we identified are the multiprofessional consultation, the reception given to residents, and the integrated actions among different majors of the residency. In addition, we identified their strategies to develop the practices in health settings. The practices follow the presuppositions of interprofessional education, as they promote the reflection of different actors on the construction of practices that aim at the provision of better healthcare for users of the Brazilian National Health System (SUS). Keywords: Interprofessional education. Permanent health education. Multiprofessional health residencies. Appreciative inquiry. Professional practice.

Burkitt's Lymphoma (BL) rarely represents the first clinical manifestation of vertical HIV infection in adolescent in Western Europe. We report the case of a 17 year-old boy with two week history of fever and enlarged cervical lymph nodes firstly misdiagnosed as EBV infection, subsequently diagnosed as Burkitt's Lymphoma and vertical HIV infection.

Background In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. Methods We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes. Results In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells. Conclusions This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.

The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6–16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA < 50 copies/ml and stable CD4 counts (>400 cells/mm 3 or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/− swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure. Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFNγ secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization.

Resumo Nosso artigo, fundamentado na Pesquisa Apreciativa, apresenta e discute as melhores práticas de um grupo de preceptores de um programa de residência multiprofissional em Saúde. As melhores práticas identificadas são: a consulta multiprofissional, o acolhimento dos residentes e as ações integradas entre as diferentes ênfases da residência. Além dessas, identificaram-se as estratégias para desenvolver as práticas nos cenários de saúde que seguem os pressupostos da educação interprofissional, já que promovem a reflexão de diferentes atores do processo na construção de práticas que buscam maior atenção à saúde dos usuários do Sistema Único de Saúde (SUS). ABSTRACT In this article, based on Appreciative Inquiry, we present and discuss the best practices of a group of preceptors from a multiprofessional health residency program in Brazil. The best practices we identified are the multiprofessional consultation, the reception given to residents, and the integrated actions among different majors of the residency. In addition, we identified their strategies to develop the practices in health settings. The practices follow the presuppositions of interprofessional education, as they promote the reflection of different actors on the construction of practices that aim at the provision of better healthcare for users of the Brazilian National Health System (SUS). Resumen Nuestro artículo, fundamentado en la investigación apreciativa, presenta y discute las mejores prácticas de un grupo de preceptores de un Programa de Residencia Multiprofesional en Salud. las mejores prácticas identificadas son: la consulta multiprofesional, la acogida de los residentes y las acciones integradas entre los diferentes énfasis de la residencia. Además de esas, se identificaron las estrategias para desarrollar las prácticas en los escenarios de Salud que siguen los supuestos de la educación interprofesional, puesto que promueven la reflexión de diferentes actores del proceso en la construcción de prácticas que buscan una mejor atención de la salud de los usuarios del Sistema Brasileño de Salud (SUS).

Subjects Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18IT

Parasites count too Parasites — and other infectious agents — can have a major impact on an ecosystem, by targeting a prominent prey or predator species. But a study of the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California suggests that parasite ecology should be given more weighty consideration in food-web analysis and ecosystem modelling in future. The surprise finding was that parasites have substantial biomass in these ecosystems, even exceeding that of top predators. For instance the biomass of trematodes — parasitic flukes — was particularly high, comparable to that of birds, fish, burrowing shrimps and polychaetes. Parasites can have strong impacts but are thought to contribute little biomass to ecosystems 1 , 2 , 3 . We quantified the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California. Here we show that parasites have substantial biomass in these ecosystems. We found that parasite biomass exceeded that of top predators. The biomass of trematodes was particularly high, being comparable to that of the abundant birds, fishes, burrowing shrimps and polychaetes. Trophically transmitted parasites and parasitic castrators subsumed more biomass than did other parasitic functional groups. The extended phenotype biomass controlled by parasitic castrators sometimes exceeded that of their uninfected hosts. The annual production of free-swimming trematode transmission stages was greater than the combined biomass of all quantified parasites and was also greater than bird biomass. This biomass and productivity of parasites implies a profound role for infectious processes in these estuaries.