Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

OBJECTIVES: To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.

Rubella antibodies in vertically and horizontally HIV-infected young adults vaccinated early in life and response to a booster dose in those with seronegative results.

BACKGROUND: Very limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life. METHODS: Prospective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards. RESULTS: Time since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels. CONCLUSION: As vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV).

INTRODUCTION: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. METHODS: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. RESULTS: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p = 0.022, Fisher's exact test). CONCLUSION: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

"I was afraid my baby would be upset with me" - women living with HIV's accounts going through non-breastfeeding in São Paulo, Brazil.

In Brazil prevention of mother to child HIV transmission guidelines recommend formula feeding. This qualitative study, carried out in a public clinic (CEADIPE/UNIFESP), aimed at exploring experiences of breastfeeding avoidance of women living with HIV living in São Paulo. Individual interviews were carried out with the support of a semi-structured questionnaire. Data was analyzed in a thematic approach with the support of AtlasTi®. During the months of January-February 2010, 25 women were interviewed, including women with (n = 12) and without previous breastfeeding experience (n = 13). Major themes identified were: Non-breastfeeding as a trigger for stigmatization, Non-breastfeeding, guilt and coping, Attitudes around non-breastfeeding for women with and without previous breastfeeding experience, and Women's support through non-breastfeeding. In conclusion women interviewed faced challenges related to HIV diagnosis, which got entangled with difficulties with breastfeeding avoidance. Different patterns of reaction and coping could be identified, regardless of mothers' previous breastfeeding experiences. Health systems were key in providing women living with HIV with tailored services and the necessary support.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

ABSTRACT Introduction: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. Methods: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. Results: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p= 0.022, Fisher's exact test). Conclusion: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Chronic meningococcemia in a vertically HIV-infected adolescent.

Chronic meningococcemia is a rare manifestation of meningococcal disease, characterized by a period of more than one week of intermittent or continuous fever, arthralgia and skin lesions without meningitis. It can occur both in previously healthy and immunocompromised patients. The gold standard for the diagnosis is culture isolation of Neisseria meningitidis in sterile material. We describe a case of a vertically HIV-infected adolescent with chronic meningococcal disease.

Self-audits as alternatives to travel-audits for improving data quality in the Caribbean, Central and South America network for HIV epidemiology.

INTRODUCTION: Audits play a critical role in maintaining the integrity of observational cohort data. While previous work has validated the audit process, sending trained auditors to sites ("travel-audits") can be costly. We investigate the efficacy of training sites to conduct "self-audits." METHODS: In 2017, eight research groups in the Caribbean, Central, and South America network for HIV Epidemiology each audited a subset of their patient records randomly selected by the data coordinating center at Vanderbilt. Designated investigators at each site compared abstracted research data to the original clinical source documents and captured audit findings electronically. Additionally, two Vanderbilt investigators performed on-site travel-audits at three randomly selected sites (one adult and two pediatric) in late summer 2017. RESULTS: Self- and travel-auditors, respectively, reported that 93% and 92% of 8919 data entries, captured across 28 unique clinical variables on 65 patients, were entered correctly. Across all entries, 8409 (94%) received the same assessment from self- and travel-auditors (7988 correct and 421 incorrect). Of 421 entries mutually assessed as "incorrect," 304 (82%) were corrected by both self- and travel-auditors and 250 of these (72%) received the same corrections. Reason for changing antiretroviral therapy (ART) regimen, ART end date, viral load value, CD4%, and HIV diagnosis date had the most mismatched corrections. CONCLUSIONS: With similar overall error rates, findings suggest that data audits conducted by trained local investigators could provide an alternative to on-site audits by external auditors to ensure continued data quality. However, discrepancies observed between corrections illustrate challenges in determining correct values even with audits.

Clinical and Laboratory Characteristics of Herpes Zoster in Patients With HIV/AIDS and Those With Juvenile Systemic Lupus Erythematosus.

BACKGROUND: HIV infection and juvenile systemic lupus erythematosus (jSLE) are risk factors for the development of herpes zoster (HZ) and its complications. Both diseases share similar immunologic aspects, such as immunodeficiency and immune activation. Therefore, our objective was to evaluate and compare the frequency and characteristics of HZ episodes in pediatric patients with HIV infection and jSLE. METHODS: A retrospective cohort study was carried out with the evaluation of 2 pediatric cohorts: HIV patients who were followed from January 1987 to December 2014 and patients with jSLE followed up from January 1990 to December 2014 in outpatient clinics. RESULTS: Of the 190 HIV patients, 48 had HZ (25.3%), with 67 episodes; of the 92 patients with jSLE, 27 had HZ (29.3%), totaling 28 episodes. The median age at the first episode of HZ was higher in the jSLE than in the HIV group (8.9 vs. 12.5 years, respectively) (P = 0.020). HIV patients were more likely to have recurrent HZ (P = 0.025). In addition, there was a tendency for HIV patients to present with disseminated HZ more frequently (P = 0.060). Although the hospitalization rate was similar between groups, patients with jSLE received intravenous acyclovir more frequently (P = 0.014). When HIV non-immune reconstitution syndrome patients were compared with jSLE group, recurrence of HZ in HIV was the only significant difference between groups (P = 0.017). CONCLUSIONS: Patients with HIV had more recurrent HZ than patients with jSLE.

Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence.

BACKGROUND: We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. METHODS: Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. RESULTS: Lower CD4 T cells and higher T cell activation and exhaustion markers were noted on CD4 T and on CD8 T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4 T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4 T and CD8 T subsets was detected. CONCLUSIONS: Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia.

Percepções acerca da importância das vacinas e da recusa vacinal numa escola de medicina / Perceptions on the importance of vaccination and vaccine refusal in a medical school

RESUMO Objetivo: Identificar a percepção da importância das vacinas e os riscos da recusa vacinal entre alunos de Medicina e médicos. Métodos: Estudo transversal realizado por meio da aplicação de questionários sobre vacinas, recusa vacinal e suas repercussões acerca da saúde pública e individual. A amostra, de 92 sujeitos, foi selecionada numa escola privada de Medicina: grupo 1 (53 estudantes do primeiro ao quarto ano) e grupo 2 (39 médicos). Os dados colhidos foram tabulados no programa Microsoft Excel e analisados estatisticamente com o teste exato de Fisher. Resultados: Os dois grupos consideram o Programa Nacional de Imunizações confiável e reconhecem a importância das vacinas, mas 64,2% dos estudantes e 38,5% dos médicos desconhecem o número de doenças infecciosas evitáveis pelas vacinas no calendário básico. A maioria dos entrevistados possuía carteira de vacinas, mas nem todos receberam vacina influenza 2015. Conheciam pessoas que recusavam vacinas e/ou recusavam vacinar seus filhos (respectivamente, 54,7 e 43,3% dos estudantes e 59,0 e 41,0% dos médicos). Dos médicos, 48,7% já atenderam pacientes que se recusaram a receber vacinas. Consideram causas de recusa vacinal: medo de eventos adversos, razões filosóficas, religiosas e desconhecimento sobre gravidade e frequência das doenças. Aspectos éticos da recusa vacinal e possibilidades legais de exigir vacinas para crianças não são consenso. Conclusões: Alunos de Medicina e médicos não se vacinam adequadamente, apresentam dúvidas sobre calendário vacinal, segurança das vacinas e recusa vacinal. Melhorar sua capacitação é importante estratégia para manter as coberturas vacinais e abordar a recusa vacinal de forma ética.

ABSTRACT Objective: To identify the perception of medical students and physicians on the importance of vaccination and the risks of vaccine refusal. Methods: Cross-sectional study with application of questionnaires about vaccines, vaccine refusal and its repercussions on public and individual health. A sample of 92 subjects was selected from a private medical school: group 1 (53 students from first to fourth grades) and group 2 (39 physicians). Data collected were tabulated in the Microsoft Excel Program and analyzed by Fisher's exact test. Results: Both groups considered the National Immunization Program reliable and recognized the importance of vaccines, but 64.2% of students and 38.5% of physicians are unaware of the vaccine-preventable infectious diseases in the basic immunization schedule. Most of the interviewees had a personal vaccine registry, but not all had received the 2015 influenza vaccine. Both groups had known people who refused vaccines for themselves or for their children (respectively, 54.7 and 43.3% of students and 59.0 and 41.0% of physicians). The total of 48.7% of physicians had already assisted vaccine refusers. Appointed causes of vaccine refusal were: fear of adverse events, philosophical and religious reasons and lack of knowledge about severity and frequency of diseases. Ethical aspects of vaccine refusal and legal possibilities of vaccine requirements for children are not consensus. Conclusions: Medical students and doctors are not adequately vaccinated and have queries about the vaccination schedule, vaccine safety and vaccine refusal. Improving these professionals' knowledge is an important strategy to maintain vaccine coverage and address vaccine refusal ethically.

PERCEPTIONS ON THE IMPORTANCE OF VACCINATION AND VACCINE REFUSAL IN A MEDICAL SCHOOL. / PERCEPÇÕES ACERCA DA IMPORTÂNCIA DAS VACINAS E DA RECUSA VACINAL NUMA ESCOLA DE MEDICINA.

OBJECTIVE: To identify the perception of medical students and physicians on the importance of vaccination and the risks of vaccine refusal. METHODS: Cross-sectional study with application of questionnaires about vaccines, vaccine refusal and its repercussions on public and individual health. A sample of 92 subjects was selected from a private medical school: group 1 (53 students from first to fourth grades) and group 2 (39 physicians). Data collected were tabulated in the Microsoft Excel Program and analyzed by Fisher's exact test. RESULTS: Both groups considered the National Immunization Program reliable and recognized the importance of vaccines, but 64.2% of students and 38.5% of physicians are unaware of the vaccine-preventable infectious diseases in the basic immunization schedule. Most of the interviewees had a personal vaccine registry, but not all had received the 2015 influenza vaccine. Both groups had known people who refused vaccines for themselves or for their children (respectively, 54.7 and 43.3% of students and 59.0 and 41.0% of physicians). The total of 48.7% of physicians had already assisted vaccine refusers. Appointed causes of vaccine refusal were: fear of adverse events, philosophical and religious reasons and lack of knowledge about severity and frequency of diseases. Ethical aspects of vaccine refusal and legal possibilities of vaccine requirements for children are not consensus. CONCLUSIONS: Medical students and doctors are not adequately vaccinated and have queries about the vaccination schedule, vaccine safety and vaccine refusal. Improving these professionals' knowledge is an important strategy to maintain vaccine coverage and address vaccine refusal ethically.

OBJETIVO: Identificar a percepção da importância das vacinas e os riscos da recusa vacinal entre alunos de Medicina e médicos. MÉTODOS: Estudo transversal realizado por meio da aplicação de questionários sobre vacinas, recusa vacinal e suas repercussões acerca da saúde pública e individual. A amostra, de 92 sujeitos, foi selecionada numa escola privada de Medicina: grupo 1 (53 estudantes do primeiro ao quarto ano) e grupo 2 (39 médicos). Os dados colhidos foram tabulados no programa Microsoft Excel e analisados estatisticamente com o teste exato de Fisher. RESULTADOS: Os dois grupos consideram o Programa Nacional de Imunizações confiável e reconhecem a importância das vacinas, mas 64,2% dos estudantes e 38,5% dos médicos desconhecem o número de doenças infecciosas evitáveis pelas vacinas no calendário básico. A maioria dos entrevistados possuía carteira de vacinas, mas nem todos receberam vacina influenza 2015. Conheciam pessoas que recusavam vacinas e/ou recusavam vacinar seus filhos (respectivamente, 54,7 e 43,3% dos estudantes e 59,0 e 41,0% dos médicos). Dos médicos, 48,7% já atenderam pacientes que se recusaram a receber vacinas. Consideram causas de recusa vacinal: medo de eventos adversos, razões filosóficas, religiosas e desconhecimento sobre gravidade e frequência das doenças. Aspectos éticos da recusa vacinal e possibilidades legais de exigir vacinas para crianças não são consenso. CONCLUSÕES: Alunos de Medicina e médicos não se vacinam adequadamente, apresentam dúvidas sobre calendário vacinal, segurança das vacinas e recusa vacinal. Melhorar sua capacitação é importante estratégia para manter as coberturas vacinais e abordar a recusa vacinal de forma ética.

Vaccine refusal - what we need to know / Recusa vacinal - que é preciso saber

Abstract Objective: Opposition to vaccines is not a new event, and appeared soon after the introduction of the smallpox vaccine in the late 18th century. The purpose of this review is to educate healthcare professionals about vaccine hesitancy and refusal, its causes and consequences, and make suggestions to address this challenge. Source of data: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and ScieLo databases from 1980 to the present day, using the terms "vaccine refusal," "vaccine hesitancy," and "vaccine confidence." The publications considered as the most relevant by the author were critically selected. Synthesis of data: The beliefs and arguments of the anti-vaccine movements have remained unchanged in the past two centuries, but new social media has facilitated the dissemination of information against vaccines. Studies on the subject have intensified after 2010, but the author did not retrieve any published studies to quantify this behavior in Brazil. The nomenclature on the subject (vaccine hesitancy) was standardized by the World Health Organization in 2012. Discussions have been carried out on the possible causes of vaccine hesitancy and refusal, as well as on the behavior of families and health professionals. Proposals for interventions to decrease public doubts, clarify myths, and improve confidence in vaccines have been made. Guides for the health care professional to face the problem are emerging. Conclusions: The healthcare professional is a key element to transmit information, resolve doubts and increase confidence in vaccines. They must be prepared to face this new challenge.

Resumo Objetivo: Oposição às vacinas não é evento novo e surgiu logo após a introdução da vacina contra varíola no fim do século XVIII. O objetivo desta revisão é esclarecer os profissionais de saúde sobre hesitação e recusa vacinal, suas causas e consequências e fazer sugestões para enfrentar esse desafio. Fonte dos dados: Foi feita busca abrangente e não sistemática nas bases de dados PubMed, Lilacs e Scielo desde 1980 até o presente, com os termos "recusa vacinal", "hesitação vacinal" e "confiança nas vacinas". Foram selecionadas de forma crítica as publicações avaliadas como mais relevantes pela autora. Síntese dos dados: As crenças e os argumentos dos movimentos antivacinas mantiveram-se inalterados nos dois últimos séculos, mas as novas mídias sociais facilitaram a disseminação das informações contra as vacinas. Os estudos sobre o assunto se intensificaram depois de 2010, mas não foram identificados estudos publicados que permitam quantificar esse comportamento no Brasil. A nomenclatura sobre o tema (hesitação vacinal) foi uniformizada pela Organização Mundial de Saúde em 2012. Pesquisas têm sido feitas sobre as possíveis causas da hesitação e recusa vacinal, e também sobre o comportamento das famílias e dos profissionais da saúde. Propostas de intervenções para diminuir as dúvidas da população, esclarecer mitos e melhorar a confiança nas vacinas têm sido feitas. Guias para o profissional de saúde enfrentar o problema estão surgindo. Conclusões: O profissional de saúde é elemento fundamental para transmitir informações, combater as dúvidas e fortalecer a confiança nas vacinas. Eles devem se preparar para enfrentar esse novo desafio.

Immune response to a Tdap booster in vertically HIV-infected adolescents.

BACKGROUND: Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. OBJECTIVE: To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). METHODOLOGY: Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Mean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52-32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0-35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88-6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3-26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. CONCLUSIONS: Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Resultados negativos na pesquisa científica: aspectos éticos / Negative results in scientific research: ethical aspects / Resultados negativos en la investigación científica: aspectos éticos

Resumo Resultados nulos, negativos ou inesperados são ocorrências possíveis para pesquisadores em todo o mundo. Não publicar tais resultados representa desperdício de recursos (de tempo, dinheiro e esforços). O objetivo deste estudo foi avaliar, mediante aplicação de questionário, o que estudantes de medicina e médicos pensam sobre a publicação de resultados inesperados ou negativos em pesquisa e discutir os aspectos éticos da questão. As questões foram respondidas por 40 alunos e 30 médicos de uma faculdade privada de medicina. Conclui-se que ainda é pouco discutida e aceita a publicação de resultados negativos ou inesperados, persistindo a crença que publicar tais resultados pode prejudicar a reputação dos pesquisadores. Quase todos os participantes acreditam ser importante a publicação desse tipo de resultados, mas apenas cerca de 60% os publicariam. Torna-se, então, importante e necessário ampliar a discussão sobre o assunto nas escolas médicas para se criar nova mentalidade acadêmica.

Abstract Null, negative or unexpected results are possible occurrences for researchers around the world. Not publishing such results is a waste of resources (time, money, and effort). The objective of this study was to evaluate, through a questionnaire, what medical students and physicians thought about the publication of unexpected or negative results in research and to discuss the ethical aspects of the matter. The questions were answered by 40 students and 30 physicians from a private medical school. It is concluded that the publication of negative or unexpected results is still insufficiently discussed and accepted, perpetuating the belief that publishing such results may harm the researchers' reputation. Almost all participants believe it is important to publish these kind of results, but only about 60% of them would publish such results. It is therefore important and necessary to broaden the discussion on this subject in medical schools to create a new academic mindset.

Resumen Los resultados nulos, negativos o inesperados son acontecimientos posibles para los investigadores en todo el mundo. No publicar tales resultados representa un desperdicio de recursos (de tiempo, dinero y esfuerzos). El objetivo de este estudio fue evaluar, a través de la aplicación de un cuestionario, qué piensan los estudiantes de medicina y los médicos sobre la publicación de resultados inesperados o negativos en la investigación y discutir los aspectos éticos de la cuestión. 40 alumnos y 30 médicos de una facultad privada de medicina respondieron al cuestionario. Se concluye que aún es poco discutida y aceptada la publicación de resultados negativos o inesperados, persistiendo la creencia de que publicar tales resultados puede perjudicar la reputación de los investigadores. Casi todos los participantes creen que es importante la publicación de este tipo de resultados, pero solo el 60% de ellos los publicaría. Se hace importante y necesario, entonces, ampliar la discusión sobre este tema en las facultades médicas para crear una nueva mentalidad académica.

Vaccine refusal - what we need to know.

OBJECTIVE: Opposition to vaccines is not a new event, and appeared soon after the introduction of the smallpox vaccine in the late 18th century. The purpose of this review is to educate healthcare professionals about vaccine hesitancy and refusal, its causes and consequences, and make suggestions to address this challenge. SOURCE OF DATA: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and ScieLo databases from 1980 to the present day, using the terms "vaccine refusal," "vaccine hesitancy," and "vaccine confidence." The publications considered as the most relevant by the author were critically selected. SYNTHESIS OF DATA: The beliefs and arguments of the anti-vaccine movements have remained unchanged in the past two centuries, but new social media has facilitated the dissemination of information against vaccines. Studies on the subject have intensified after 2010, but the author did not retrieve any published studies to quantify this behavior in Brazil. The nomenclature on the subject (vaccine hesitancy) was standardized by the World Health Organization in 2012. Discussions have been carried out on the possible causes of vaccine hesitancy and refusal, as well as on the behavior of families and health professionals. Proposals for interventions to decrease public doubts, clarify myths, and improve confidence in vaccines have been made. Guides for the health care professional to face the problem are emerging. CONCLUSIONS: The healthcare professional is a key element to transmit information, resolve doubts and increase confidence in vaccines. They must be prepared to face this new challenge.

Immune response to a Tdap booster in vertically HIV-infected adolescents

Background Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. Objective To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). Methodology Thirty HIV adolescents with CD4 cell counts?>200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. Results Mean age of HIV and CONTROL groups were 17.9 e 17.1?years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28?days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28?days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p?=?.002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-?) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. Conclusions Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Immune response to a Tdap booster in vertically HIV-infected adolescents

Background Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. Objective To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). Methodology Thirty HIV adolescents with CD4 cell counts?>200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. Results Mean age of HIV and CONTROL groups were 17.9 e 17.1?years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28?days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28?days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p?=?.002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-?) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. Conclusions Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Immune development in HIV-exposed uninfected children born to HIV-infected women.

Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1ß levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Bone mineral density and vitamin D concentration: the challenges in taking care of children and adolescents infected with HIV

ABSTRACT Background: The increase in life expectancy for patients living with human immunodeficiency virus (HIV) infection has resulted in health complications related to a chronic disease. Objectives: To evaluate the prevalence of bone mineral density (BMD) alterations and vitamin D concentrations in HIV-infected children and adolescents and to verify the variations in those parameters during a 12-month interval. Methods: A prospective cohort study with a dual period of evaluation was conducted in 57 patients perinatally HIV-infected and one patient with sexual abuse in early infancy. Demographic, anthropometric, pubertal stage, viral load, T CD4+ cell count and antiretroviral therapy were evaluated. Biochemical tests and total body (TB) and lumbar spine (L1-L4) bone density evaluations by dual X-ray absorptiometry (DXA) were performed. Calcium or vitamin D supplements were prescribed if reduction in BMD or deficiency for vitamin D was detected. Results: 58 patients (ages 5.4-18.3 years; 60.3% girls) were included (T0); 55 patients were reevaluated after 12 (±3) months (T1). Low bone mass for chronological age was found in 6/58 (10.4%) and 6/55(10.9%) patients at T0 and at T1, respectively. There was no statistical relationship between z-scores for BMD (BMD z-score) and the variables sex, fracture history, family history of osteoporosis, physical activity and pubertal stage. There was a relation between BMD z-score alterations for TB and HIV viral load at T1 (p = 0.016). There was no association between duration or classes of antiretroviral therapy and bone density. The mean value of vitamin D in T0 was 23.43 ng/mL ± 2.015 and in T1 22.1 ng/mL ± 0.707 and considered insufficient levels for this population. Conclusion: Patients infected with HIV are at risk for BMD alterations and lower vitamin D serum concentrations; both of these variables should be evaluated at routine examinations in order to improve both prevention and therapeutic planning.

Bone mineral density and vitamin D concentration: the challenges in taking care of children and adolescents infected with HIV.

BACKGROUND: The increase in life expectancy for patients living with human immunodeficiency virus (HIV) infection has resulted in health complications related to a chronic disease. OBJECTIVES: To evaluate the prevalence of bone mineral density (BMD) alterations and vitamin D concentrations in HIV-infected children and adolescents and to verify the variations in those parameters during a 12-month interval. METHODS: A prospective cohort study with a dual period of evaluation was conducted in 57 patients perinatally HIV-infected and one patient with sexual abuse in early infancy. Demographic, anthropometric, pubertal stage, viral load, T CD4+ cell count and antiretroviral therapy were evaluated. Biochemical tests and total body (TB) and lumbar spine (L1-L4) bone density evaluations by dual X-ray absorptiometry (DXA) were performed. Calcium or vitamin D supplements were prescribed if reduction in BMD or deficiency for vitamin D was detected. RESULTS: 58 patients (ages 5.4-18.3 years; 60.3% girls) were included (T0); 55 patients were reevaluated after 12 (±3) months (T1). Low bone mass for chronological age was found in 6/58 (10.4%) and 6/55(10.9%) patients at T0 and at T1, respectively. There was no statistical relationship between z-scores for BMD (BMD z-score) and the variables sex, fracture history, family history of osteoporosis, physical activity and pubertal stage. There was a relation between BMD z-score alterations for TB and HIV viral load at T1 (p=0.016). There was no association between duration or classes of antiretroviral therapy and bone density. The mean value of vitamin D in T0 was 23.43ng/mL±2.015 and in T1 22.1ng/mL±0.707 and considered insufficient levels for this population. CONCLUSION: Patients infected with HIV are at risk for BMD alterations and lower vitamin D serum concentrations; both of these variables should be evaluated at routine examinations in order to improve both prevention and therapeutic planning.