Impact of six years of routine varicella vaccination on the disease-related hospitalizations at Minas Gerais, Brazil.

INTRODUCTION: The varicella vaccine was first introduced into the Brazilian immunization schedule in September 2013 as a single dose for children aged 15 months. In 2018, a second dose was recommended for individuals between 4 and 6 years old. This study aims to assess the impact of routine varicella vaccination on the number and profile of hospitalized varicella patients during the single dose period, as well as in the first two years after the adoption of the second dose. METHODS: An observational retrospective study was conducted in an infectious disease pediatric hospital, in Minas Gerais, Brazil. Clinical as well as epidemiological data from patients hospitalized due to varicella between 2010 and 2019 were collected. Patients were split into groups based on the vaccine introduction: pre-vaccine period, single dose and two-dose period. They were compared by age, sex, reason for admission, illness-related complications and clinical outcome. RESULTS: There were 1193 admissions due to varicella during the studied period. When compared with the pre-vaccine period, the number of hospitalizations decreased in 61.5% during the single-dose regime, reaching 95.2% in the two-dose period. Hospitalization rates decreased in all age groups, including non-vaccinated individuals such as those younger than 12 months (92.1%). As for reasons of admission, secondary bacterial skin infections were perceived to be the most common cause (>70%). A reduction was also seen in admission of immunocompromised or HIV positive patients (84.8%). CONCLUSION: The collected data shows a significant impact in the number of hospital admissions due to varicella after six years of the implementation of the vaccine, positively affecting both vaccinated and non-vaccinated individuals. Further reduction was seen after the second dose was initiated, but its true impact will only be understood fully after a longer period of continuous vaccination.

Anemia and nutritional aspects in adolescent athletes: a cross-sectional study in a reference sport organization / Anemia e aspectos nutricionais em atletas adolescentes: estudo transversal em agremiação desportiva de referência nacional

ABSTRACT Objective: To assess the association between anemia and nutritional aspects in adolescent athletes from a large sport club. Methods: This is a cross-sectional study, involving 298 athletes aged between 10 and 17 years, submitted to measurement of skin folds, weight and height, and collection of capillary blood in duplicate to determine hemoglobin values. It was carried out in a random sample composed of athletes from eight sport modalities. Results: Regarding nutritional status, 10.1% of athletes were overweight based on body mass index and 70 (23.5%) athletes had a percentage of body fat classified as high or very high. The prevalence of anemia was 16.4%, being more prevalent in judo (37.1%), basketball (34%) and futsal (20.5%) athletes. Low hemoglobin levels were significantly associated with shorter stature (p=0.006). Conclusions: There was a significant association between anemia and short stature, suggesting that the athlete's height-weight development may be affected in suboptimal conditions of oxygen distribution.

RESUMO Objetivo: Avaliar a associação entre anemia e aspectos nutricionais em atletas adolescentes de um clube desportivo de grande porte. Métodos: Trata-se de estudo de corte transversal que envolveu 298 atletas com idades entre 10 e 17 anos, submetidos à aferição de dobras cutâneas, peso e altura, além de coleta de sangue capilar em duplicata para a determinação dos valores de hemoglobina. Foi realizado em amostra aleatória composta de atletas oriundos de oito modalidades esportivas. Resultados: Em relação ao estado nutricional, 10,1% dos atletas apresentaram excesso de peso com base no índice de massa corpórea e 70 (23,5%) atletas estavam com porcentagem de gordura corporal classificada como alta ou muito alta. A prevalência de anemia foi de 16,4%, mais prevalente nos atletas do judô (37,1%), basquete (34%) e futsal (20,5%). Níveis baixos de hemoglobina foram associados à menor estatura (p=0,006). Conclusões: Observou-se associação significativa entre anemia e baixa estatura, o que sugere que o desenvolvimento pôndero-estatural do atleta pode ser afetado em condições subótimas de distribuição de oxigênio.

Anemia and nutritional aspects in adolescent athletes: a cross-sectional study in a reference sport organization.

OBJECTIVE: To assess the association between anemia and nutritional aspects in adolescent athletes from a large sport club. METHODS: This is a cross-sectional study, involving 298 athletes aged between 10 and 17 years, submitted to measurement of skin folds, weight and height, and collection of capillary blood in duplicate to determine hemoglobin values. It was carried out in a random sample composed of athletes from eight sport modalities. RESULTS: Regarding nutritional status, 10.1% of athletes were overweight based on body mass index and 70 (23.5%) athletes had a percentage of body fat classified as high or very high. The prevalence of anemia was 16.4%, being more prevalent in judo (37.1%), basketball (34%) and futsal (20.5%) athletes. Low hemoglobin levels were significantly associated with shorter stature (p=0.006). CONCLUSIONS: There was a significant association between anemia and short stature, suggesting that the athlete's height-weight development may be affected in suboptimal conditions of oxygen distribution.

NUMBER OF CASES OF VARICELLA AND HOSPITALIZATION IN A PEDIATRIC REFERENCE HOSPITAL IN BRAZIL AFTER INTRODUCING THE VACCINE.

OBJECTIVE: To assess the number of cases and the profile of hospitalizations from varicella after the introduction of the measles, mumps, rubella and varicella combination vaccine in the public health system. METHODS: Retrospective study in an infectious diseases pediatric hospital of reference in Southeast Brazil. The cases with a clinical diagnosis of varicella, from January 2011 to June 2016, were assessed from pediatricians' medical records. The hospitalizations were classified into a pre-vaccine group and post-vaccine group, based on the date the vaccine was introduced (September 2013). Both groups were compared by age, sex, time of hospitalization, reason for hospitalization, hospital complications, duration of intensive care, and clinical outcome. RESULTS: A total of 830 hospitalizations were recorded; 543 in the pre-vaccine period and 287 in the post-vaccine period, a reduction of 47.1% (p<0.001). In both periods, a similar profile in the hospitalizations was noticed: majority male; aged between one to five years old; most complications due to secondary causes (mainly skin infections); main outcome was clinical improvement and discharge from the hospital. In the pre-vaccine period, six deaths were recorded and two were recorded in the post-vaccine period. CONCLUSIONS: The profile of the hospitalizations was expected to stay the same since this study did not compare vaccinated with unvaccinated children, but hospitalizations before and after the vaccine was introduced. In accordance with the medical literature, we found a significant fall in the number of hospitalizations from varicella.

Number of cases of varicella and hospitalization in a pediatric reference hospital in brazil after introducing the vaccine / Avaliação do número de casos e do perfil de internações por varicela em hospital pediátrico após a introdução da vacina

ABSTRACT Objective: To assess the number of cases and the profile of hospitalizations from varicella after the introduction of the measles, mumps, rubella and varicella combination vaccine in the public health system. Methods: Retrospective study in an infectious diseases pediatric hospital of reference in Southeast Brazil. The cases with a clinical diagnosis of varicella, from January 2011 to June 2016, were assessed from pediatricians' medical records. The hospitalizations were classified into a pre-vaccine group and post-vaccine group, based on the date the vaccine was introduced (September 2013). Both groups were compared by age, sex, time of hospitalization, reason for hospitalization, hospital complications, duration of intensive care, and clinical outcome. Results: A total of 830 hospitalizations were recorded; 543 in the pre-vaccine period and 287 in the post-vaccine period, a reduction of 47.1% (p<0.001). In both periods, a similar profile in the hospitalizations was noticed: majority male; aged between one to five years old; most complications due to secondary causes (mainly skin infections); main outcome was clinical improvement and discharge from the hospital. In the pre-vaccine period, six deaths were recorded and two were recorded in the post-vaccine period. Conclusions: The profile of the hospitalizations was expected to stay the same since this study did not compare vaccinated with unvaccinated children, but hospitalizations before and after the vaccine was introduced. In accordance with the medical literature, we found a significant fall in the number of hospitalizations from varicella.

RESUMO Objetivo: Avaliar o número de casos e o perfil das internações por varicela após a introdução da vacina quádrupla viral na rede pública. Métodos: Estudo retrospectivo conduzido em hospital pediátrico referência em doenças infectocontagiosas na Região Sudeste do Brasil. Foram avaliados os casos com diagnóstico clínico de varicela, registrados em prontuário por médico pediatra, de janeiro de 2011 até junho de 2016. As internações foram classificadas em grupo pré-vacinal e grupo pós-vacinal, com base na data de introdução da vacina (setembro de 2013). Os grupos foram comparados em relação a: faixa etária, sexo, tempo de hospitalização, causas da internação, complicações hospitalares, tempo da internação em terapia intensiva e desfecho clínico. Resultados: Foram documentadas 830 internações, 543 no período pré-vacinal e 287 no pós-vacinal, ocorrendo redução de 47,1% nas internações (p<0,001). Em ambos os períodos, notou-se um perfil similar das internações, predominantemente: sexo masculino; faixa etária de um a cinco anos; por causas secundárias (principalmente infecções de pele); evoluindo com melhora clínica e alta hospitalar. Em relação ao número de óbitos, ocorreram seis no período pré-vacinal e dois no pós-vacinal. Conclusões: A manutenção do perfil das internações era esperada, visto que o trabalho não comparou crianças vacinadas com não vacinadas, e sim internações pré e pós-vacinais. Observou-se, em concordância com a literatura, queda substancial no número de internações por varicela.

Yellow fever in children and adolescents previously immunized in Minas Gerais State, Brazil.

Background - Yellow fever (YF) is a viral hemorrhagic fever that is transmitted by arthropods. It can occur with little symptomatic manifestations to the most fulminant forms. The most effective way to avoid YF is through vaccination. There is a lack of information about the immune response of the vaccine in childhood. Methods - We described children and adolescents with YF who had been previously immunized in Minas Gerais State from July 2017 to June 2018. Results - 527 cases of YF were observed representing an incidence of 7.6/100,000 inhabitants. Only 26 patients (4.9%) were ≤ 20 years and 501 (95.1%) were > 20 years. Only 9 vaccinated patients were ≤ 20 years and 15 were > 20 years. 34.6% (9/26) of YF patients ≤ 20 years were previously vaccinated and 3% (15/501) of those > 20 years (p < 0.001). The median age at vaccination was 1 year between those ≤ 20 years and 31 years between those > 20 years (p = 0.002). Among 9 vaccinated children and adolescents ≤ 20 years, age ranged from 7 to 18 years, the most described symptoms were fever (88%), headache (77%), myalgia (77%), and abdominal pain (66%). All patients recovered from the disease and none died. Conclusion - Prior YF vaccination may be associated with mild forms of the disease in children and adolescents. YF vaccination in the first years of life may be associated with poor vaccine response and high infection rates in this group as it fail to seroconvert a significant proportion of infants.

Short-Lived Immunity After 17DD Yellow Fever Single Dose Indicates That Booster Vaccination May Be Required to Guarantee Protective Immunity in Children.

The Yellow Fever (YF) vaccination is recommended for people living in endemic areas and represents the most effective strategy to reduce the risk of infection. Previous studies have warned that booster regimens should be considered to guarantee the long-term persistence of 17DD-YF-specific memory components in adults living in areas with YF-virus circulation. Considering the lower seroconversion rates observed in children (9-12 months of age) as compared to adults, this study was designed in order to access the duration of immunity in single-dose vaccinated children in a 10-years cross-sectional time-span. The levels of neutralizing antibodies (PRNT) and the phenotypic/functional memory status of T and B-cells were measured at a baseline, 30-45 days, 1, 2, 4, 7, and 10 years following primary vaccination. The results revealed that a single dose induced 85% of seropositivity at 30-45 days and a progressive time-dependent decrease was observed as early as 2 years and declines toward critical values (below 60%) at time-spans of ≥4-years. Moreover, short-lived YF-specific cellular immunity, mediated by memory T and B-cells was also observed after 4-years. Predicted probability and resultant memory analysis emphasize that correlates of protection (PRNT; effector memory CD8+ T-cells; non-classical memory B-cells) wane to critical values within ≥4-years after primary vaccination. Together, these results clearly demonstrate the decline of 17DD-YF-specific memory response along time in children primarily vaccinated at 9-12 months of age and support the need of booster regimen to guarantee the long-term persistence of memory components for children living in areas with high risk of YF transmission.

17DD Yellow Fever Revaccination and Heightened Long-Term Immunity in Populations of Disease-Endemic Areas, Brazil.

We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine-specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-γ+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-γ+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF-specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.

Prevenção de Infecções pelo Vírus Sincicial Respiratório (VSR): uso do palivizumabe / Respiratory Syncytial Vírus (RSV) infection prevention: palivizumab use

Introdução: o vírus sincicial respiratório (VSR) pode causar quadros graves de bronquiolites e pneumonias, principalmente em grupos de risco como prematuros, cardiopatas e portadores de pneumopatias. O palivizumabe (PVZ) trouxe grande avanço na prevenção dessa doença e, devido ao alto custo, a Secretaria de Estado da Saúde de Minas Gerais (SES-MG) disponibiliza o produto aos grupos de alto risco. Objetivo: orientar os pediatras quanto à prevenção da infecção pelo VSR com orientações práticas sobre a prescrição do PVZ em MG. Métodos: são apresentados os critérios de inclusão para o uso dessa medicação em MG segundo portaria do Ministério da Saúde de 2013, como também os procedimentos adequados para a prescrição e fornecimento segundo normas da SES-MG. Resultados e conclusões: o conhecimento sobre o uso do PVZ para a prevenção do VSR e dos fluxos adequados para a prescrição e aplicação dessa medicação é fundamental para a prevenção da bronquiolite, portanto, deve ser amplamente divulgado entre os pediatras. Dessa forma, poderá ocorrer a redução dos casos graves, diminuindo a prevalência de sequelas e óbitos por essa doença.(AU)

Introduction: Respiratory Syncytial Vírus (RSV) can cause severe cases of bronchiolitis and pneumonia especially in risk groups such as premature neonates, cardiac patients and children with lung disease. Palivizumab (PVZ) has been successfully used in the prevention of this disease and due to the high cost, the Health's Secretary of Minas Gerais (SESMG) provides the product to high-risk groups. Objective: guide pediatricians regarding the prevention of RSV infection with practical guidelines for the prescription of PVZ in MG. Methods: Here are the inclusion criteria for the application of this medication in MG following the guidelines of the Ministry of Health in 2013, as well as the proper procedures for the prescription and supply according to standards of SES-MG. Results and Conclusions: Knowledge about the use of PVZ for the prevention of RSV and about the guidelines for prescription and application of this medication are key to the prevention of bronchiolitis, therefore should be widely disseminated to pediatricians. Thus may occur the reduction of severe cases decreasing the prevalence of sequelae and deaths from this disease.(AU)

Avaliação da cobertura vacinal em crianças de um a dois anos pelo Monitoramento Rapido de Cobertura em Vespasiano / Evaluation of vaccination coverage in children one to two year old using the Fast Coverage Monitoring Method in the city of Vespasiano

Introdução:A cobertura vacinal pode ser determinada por três métodos distintos: administrativo, inquérito e o Monitoramento Rápido de Cobertura (MRC). No Brasil, o método mais utilizado é o administrativo. Porém, considerando-se a heterogeneidade nos resultados, o Ministério da Saúde institucionalizou o MRC como a principal ferramenta para verificação rotineira da situação vacinal. Este estudo avaliou se as coberturas para tetravalente, febre amarela e influenza estavam de acordo com o preconizado pelo Programa Nacional de Imunizações a partir da realização de um MRC. Trata-se de um estudo populacional descritivo. Métodos:O cálculo amostral baseou-se no Protocolo de MRC do Ministério da Saúde e constituiu-se de crianças de 1 a 2 anos, residentes em áreas de abrangência de duas unidades de saúde do bairro Célvia, em Vespasiano. Resultados:A cobertura encontrada para febre amarela e tetravalente no Célvia 1 foi de 100% e no Célvia 2 de 96%. Em relação à influenza, a cobertura variou de 68% no Célvia 1 a 75% no Célvia 2. Não houve diferença estatística significativa entre os valores, com p variando de 0,754 a 1,000. Conclusão:As coberturas obtidas pelo Monitoramento Rápido de Cobertura para as vacinas febre amarela e tetravalente em ambas as áreas estudadas corresponderam à meta operacional preconizada pelo PNI (95%). Em relação à vacina Influenza, observou-se cobertura vacinal abaixo do recomendado (80%) nas duas unidades de saúde. Embora não seja possível fazer uma comparação estatística, observou-se diferença entre a cobertura administrativa e o MRC em relação à vacina Influenza.

Introduction:Vaccination coverage can be determined through three different methods: Administrative, Baseline Study and rapid Monitoring of Vaccination Coverage (MVC). From those, Administrative method is the most used in Brazil. However, due to heterogeneity in vaccination coverage results, MVC was recommended by the Ministry of Health as a supervisory tool to verify vaccination status. This population-based descriptive study aimed at evaluating if vaccination coverage for tetravalent, yellow fever and influenza vaccines were in accordance with Brazil's National Immunization Program (NIP) recommendations when MVC was used. Method:Sample calculation, having the MVC Protocol from the Ministry of Health as a basis, included children aged 1 to 2 years old, who lived in areas covered by two different outpatient care units (Célvia 1 and Célvia 2) in Célvia neighborhood, Vespasiano, Brazil. Results:Yellow fever and MMR vaccines coverage was 100% at Célvia 1 and 96% at Célvia 2. Influenza coverage has varied from 68% at Célvia 1 to 75% at Célvia 2. Those values showed no significant statistical difference, with p-value varying from 0.754 to 1.000. Conclusion:Use of MVC at Célvia 1 and Célvia 2 showed that yellow fever and tetravalent vaccines coverage reached NIP target (95%). A different result was shown for influenza vaccine, whose coverage was under the recommended target (80%) in both outpatient care units. A difference between administrative coverage and MVC was found, although a statistical comparison is not possible.

17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children.

BACKGROUND: This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF) substrains. METHODS: A non-probabilistic sample of eighty healthy primary vaccinated (PV) children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT) and referred to as seroconverters (PV-PRNT(+)) or nonseroconverters (PV-PRNT(-)). Following revaccination with the YF-17DD, the PV-PRNT(-) children (YF-17D-213/77 and YF-17DD groups) seroconverted and were referred as RV-PRNT(+). The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control) as the cut-off. RESULTS: The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+), with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+) in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+)CD8(+) T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(-) children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+)T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D-213/77 nonresponders. CONCLUSION: Our findings demonstrated that, just like the YF-17DD reference vaccine, the YF-17D-213/77 seed lot induced a mixed pattern of inflammatory and regulatory cytokines, supporting its universal use for immunization.

Characterization of main cytokine sources from the innate and adaptive immune responses following primary 17DD yellow fever vaccination in adults.

The mechanisms of immune response following yellow fever (YF-17DD) vaccination are still poorly understood. In this study, we have performed a longitudinal investigation (days 0, 7, 15 and 30) to characterize the cytokine profile of innate and adaptive immunity following YF-17DD first-time vaccination. Data from non-stimulated cultures demonstrated a prominent participation of the innate immunity with increased frequency of TNF-α(+) neutrophils and IFN-γ(+) NK-cells at day 7 besides TNF-α(+) monocytes at day 7, day 15 and day 30. Increased frequency of IL-10(+) monocytes was observed at day 15 and day 30, and decreased percentage of IL-4(+) NK-cells were detected at day 7, day 15 and day 30. Time-dependent and oscillating cytokine pattern was observed in CD4(+) T-cells, with low percentage of IL-12(+), IL-4(+) and IL-10(+) cells at day 7 and increased frequency of TNF-α(+) cells at day 15 besides IFN-γ(+) and IL-5(+) cells at day 15 and day 30. Later changes with increased percentage of IL-12(+) and IL-5(+)CD8(+) T-cells were observed at day 30. Increased frequency of IL-10(+) B-cells was observed at day 15, when seroconversion was detected in all vaccinees. The overall cytokine analysis of non-stimulated leukocytes showed a transient shift towards a pro-inflammatory profile at day 7, mainly due to changes in the innate immunity, which draws back toward a mixed/regulatory pattern at day 15 and day 30. The changes induced by the in vitro YF-17DD vaccine-stimulation were mainly observed at day 0 and day 7 (before seroconversion) with minor changes at day 15 and day 30 (after seroconversion). These data support the hypothesis that a complex network with mixed pro/anti-inflammatory cytokine profile is associated with the establishment of the protective immunity following YF-17DD primo-vaccination, free of adverse events.

Innate immunity phenotypic features point toward simultaneous raise of activation and modulation events following 17DD live attenuated yellow fever first-time vaccination.

Detailed multiparametric phenotypic investigation aiming to characterize the kinetics of the innate immune response in the peripheral blood following 17DD yellow fever (17DD-YF) first-time vaccination was performed. Results showed increased frequency of monocytes and NK cell subpopulations besides unexpected up-regulation of granulocytes activation status (CD28+/CD23+ and CD28+/HLA-DR+, respectively). Up-regulation of Fcgamma-R and IL-10-R expression emerge as putative events underlying the mixed pattern of phenotypic features triggered by the 17DD yellow fever (17DD-YF) vaccination. Mixed pattern of chemokine receptors expression further support our hypothesis that a parallel establishment of activation/modulation microenvironment plays a pivotal role in the protective immunity triggered by the 17DD-YF vaccine.

Aspectos médico-sociais da gravidez na adolescência nos últimos 20 anos: uma revisão da literatura / Medical-social aspects of pregnancy in adolescence in the last 20 years: a review of literature

Contracepção e gravidez precoce são questões importantes enfrentadas por médicos e educadores ao longo de suas carreiras. Gravidez na adolescência é problema médico-social grave. É preciso conhecer suas causas, conseqüências e complicações. Este trabalho resulta de uma revisão de publicações sobre gravidez precoce no período de 1980 a 2000. As bases de dados utilizadas foram Medline, adolec e busca direta. Objetiva-se atualizar, orientar e esclarecer dúvidas dos profissionais a respeito desses fatores.

Contraception and pronatis pregnancy are important factors faced by physicians and educators throughout their careers. The pregnancy in the adolescence is a serious medical-social problem. It's necessary to know itsmain causes, consequences and complications. This study results from a publication review about premature pregnancy from 1980 to 2000. This review is based on Medline, Adolec sites and direct search. The major targets are updating, guiding and enlightening the doubts from professionals regarted to these factors.

Descriçäo clínica de três casos com comprovaçäo sorológica de febre maculosa / Clinical description of three cases with spotted fever serological confirmation

Os autores fazem breve relato da história e da situaçäo atual da Febre Maculosa em Minas Gerais. Em seguida descrevem o quadro clínico de três pacientes acometidos pela doença. Nos comentários discutem os sinais e sintomas apresentados pelos pacientes, em comparaçäo com o descrito na literatura.