Encefalite anti-receptor N-metil-D-aspartato na infância

OBJETIVO: Discutir o diagnóstico diferencial das encefalites além daquelas de etiologia infecciosa, e alertar os pediatras para a possibilidade do diagnóstico de encefalite anti-receptor N-metil-D-aspartato (rNMDA) na população pediátrica, destacando suas principais características clínicas. DESCRIÇÃO: Três pacientes apresentaram-se com uma síndrome neuropsiquiátrica inicial seguida de encefalopatia e transtornos de movimento. As características neuropsiquiátricas iniciais se desenvolveram ao longo de dias ou semanas, com mudanças comportamentais, ansiedade, confusão mental e regressão da fala. Em seguida, os pacientes evoluíram com distúrbios de movimento, caracterizados por coreoatetose ou distonia, acometendo a região orofacial e os membros. Após a exclusão das principais causas de encefalite, foram identificados anticorpos anti-rNMDA no soro e no líquido cefalorraquidiano. Não foram detectadas neoplasias durante a investigação etiológica. Os pacientes foram submetidos a imunossupressão, e dois deles tiveram uma recuperação neurológica completa. Um deles ainda apresenta uma postura distônica leve em um dos membros. COMENTÁRIOS: Os sinais clínicos de encefalite anti-rNMDA em crianças são semelhantes aos anteriormente descritos em adultos. Tumores geralmente não são detectados nessa idade. O diagnóstico de encefalite anti-rNMDA deve ser abordado após a exclusão de outras causas de encefalite na infância, como as de origem infecciosa. Pediatras devem estar atentos a essa condição autoimune passível de tratamento.

Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects

Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, precise diagnosis of MODY is important for determining management and prognosis. We report two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and negative beta-cell antibodies. His father and two siblings also had slightly elevated blood glucose levels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); beta-cell antibodies were negative. His father, a paternal aunt, and the paternal grandmother also had slightly elevated glycemia, whereas his mother had normal glycemia. A GCK heterozygous missense mutation, p.Glu221Lys, was identified in the index patient and in four family members. All affected patients had mild elevated glycemia. Individuals with normal glycemia did not harbor mutations. GCK mutation screening should be considered in patients with chronic mild early-onset hyperglycemia, family history of impaired glycemia, and negative beta-cell antibodies. Arq Bras Endocrinol Metab. 2012;56(8):519-24

Canine distemper virus and Toxoplasma gondii co-infection in dogs with neurological signs

O presente estudo relata a ocorrência de co-infecção entre o vírus da cinomose canina (CDV) e Toxoplama gondii em cães com sinais neurológicos. Amostras de soro e tecido nervoso (pos-mortem) de 21 cães, suspeitos de cinomose canina foram analisadas pela Reação de Imunofluorecência indireta (RIFI) para pesquisa de anticorpos contra T. gondii e N. caninum e por RT-PCR para CDV. Dezessete (80,9%) cães foram positivos para o CDV pela RT-PCR e 8 (38,1%) foram positivos para anticorpos contra T. gondii. Sete cães (41,1%) apresentaram-se positivos para ambos agentes, caracterizando processo de co-infecção. Somente 1 (4,7%) cão foi soropositivo para N. caninum (RIFI=100), entretanto este mesmo animal foi positivo para T. gondii (RIFI=4096) e para CDV (RT-PCR).

Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth

The aim of this study was to evaluate the immunoexpression of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth and to correlate the results with demographic, survival, clinical (TNM staging) and histopathological variables (tumor grade, perineural invasion, embolization and bone invasion). Data from medical records and diagnoses of 41 patients were reviewed. Histological sections were subjected to immunostaining using primary antibodies for human MMP-2, MMP-9 and CD31 and streptavidin-biotin-immunoperoxidase system. Histomorphometric analyses quantified positivity for MMPs (20 fields per slide, 100?points grade, ×200) and for CD31 (microvessels <50?µm in the area of the highest vascularization, 5 fields per slide, 100?points grade, ×400). Statistical design was composed by non-parametric Mann-Whitney U test (investigating the association between numerical variables and immunostainings), chi-square frequency test (in contingency tables), Fisher's exact test (when at least one expected frequency was less than 5 in 2×2 tables), Kaplan-Meier method (estimated probabilities of overall survival) and Iogrank test (comparison of survival curves), all with a significance level of 5%. There was a statistically significant correlation between immunostaining for MMP-2 and lymph node metastasis. Factors associated negatively with survival were N stage, histopathological grade, perineural invasion and immunostaining for MMP-9. There was no significant association between immunoexpression of CD31 and the other variables. The intensity of immunostaining for MMP-2 can be indicative of metastasis in lymph nodes and for MMP-9 of a lower probability of survival

A serological follow-up of toxocariasis patients after chemotherapy based on the detection of IgG, IgA, and IgE antibodies by enzyme-linked immunosorbent assay.

A serological follow-up study was carried out on 27 children (1–12 years old) with visceral and/or ocular toxocariasis, after treatment with thiabendazole. A total of 159 serum samples were collected in a period ranging from 22–116 months. Enzyme-linked immunosorbent assays (IgG, IgA, and IgE ELISA) were standardized, using excretory–secretory antigens obtained from the second-stage larvae of a Toxocara canis culture. The sensitivity found for the IgG, IgA, and IgE ELISA, as determined in visceral toxocariasis patients, was 100%, 47.8%, and 78.3%, respectively. Approximately 84% of the patients presented single or multiple parasitosis, as diagnosed by stool examination, yet such variables did not appear to affect the anti-Toxocara immune response. Titers of specific IgE antibody showed a significant decrease during the first year after treatment, followed by a decrease in the IgA titers in the second year, and in the IgG titers from the fourth year onwards. Sera from all patients presented high avidity IgG antibodies, indicating that they were in the chronic phase of the disease. Moreover, 1 year after treatment, the level of leukocytes, eosinophils, and anti-A isohemagglutinin in patients decreased significantly. The present data suggest that IgE antibodies plus eosinophil counts are helpful parameters for patient followup after chemotherapy.

Treatment of neuromyelitis optica: an evidence based review

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

Análise crítica das recomendações do uso das vacinas meningocócicas conjugadas

OBJETIVOS: Analisar a epidemiologia da doença meningocócica no Brasil e o impacto que as recentes evidências acumuladas com a incorporação das vacinas meningocócicas C conjugadas nos programas de imunização podem ter nas diferentes estratégias de uso dessas vacinas. FONTES DOS DADOS: Revisão nas bases de dados MEDLINE, SciELO e LILACS no período de 2000 a 2011. SÍNTESE DOS DADOS: No Brasil, a doença meningocócica é endêmica, com ocorrência periódica de surtos. Os maiores coeficientes de incidência ocorrem em lactentes, sendo o sorogrupo C responsável pela maioria dos casos, motivando a introdução da vacina meningocócica C conjugada no Programa Nacional de Imunizações, em 2010, para crianças menores de 2 anos. A introdução das vacinas meningocócicas C conjugadas nos programas de imunização na Europa, Canadá e Austrália mostrou-se efetiva, com dramática redução na incidência de doença causada pelo sorogrupo C, não apenas nos vacinados, mas também em não vacinados. A efetividade em longo prazo dessas vacinas mostrou-se dependente de uma combinação de persistência de anticorpos, memória imunológica e proteção indireta. Recentes evidências indicando que a persistência de anticorpos não é duradoura em crianças pequenas imunizadas e que a memória imunológica não é rápida o suficiente para protegê-las contra a doença enfatizam a importância da proteção indireta para manutenção da população protegida. CONCLUSÕES: A rápida queda de títulos de anticorpos em crianças vacinadas nos primeiros anos de vida sugere a necessidade de incorporarmos doses de reforço antes da adolescência, especialmente em locais como o Brasil, onde ainda não contamos com o efeito da proteção indireta da população.

IgG Antibody responses in mice coinfected with Toxocara canis and other helminths or protozoan parasites

The immune response expressed by IgG antibodies in BALB/c mice experimentally infected with Toxocara canis, was studied with the aim of verifying the possible in vivo cross-reactivity between antigens of T. canis and other parasites (Ascaris suum, Taenia crassiceps, Schistosoma mansoni, Strongyloides venezuelensis and Toxoplasma gondii). Experiments included three groups of mice: one infected only by T. canis, another with one of the other species of parasites and a third concomitantly infected with T. canis and the other species in question. Animals were bled by orbital plexus at 23, 38 and 70 days post infection (p.i.). Sera were analyzed for anti-Toxocara antibodies by ELISA and Immunoblotting, using excretion-secretion antigens (ES), obtained from culture of third-stage larvae of T. canis. For all experiments a control group comprised by ten non-infected mice was used. Only in the case of A. suum infection, in these experimental conditions, the occurrence of cross-reactivity with T. canis was observed. However, in the case of co-infection of T. canis - S. mansoni, T. canis - S. venezuelensis and T. canis - T. crassiceps the production of anti-Toxocara antibodies was found at levels significantly lower than those found in mice infected with T. canis only. Co-infection with S. mansoni or S. venezuelensis showed lower mortality rates compared to what occurred in the animals with single infections. Results obtained in mice infected with T. canis and T. gondii showed significant differences between the mean levels of the optical densities of animals infected with T. canis and concomitantly infected with the protozoan only in the 23rd day p.i.

Antibody levels to hantavirus in inhabitants of western Santa Catarina State, Brazil

Hantavirus cardiopulmonary syndrome (HCPS) is an infectious disease caused by hantaviruses of the family Bunyaviridae, and is transmitted by aerosols of excreta of infected rodents. The aim of the present study was to determine antibody levels to hantavirus in the population that lives at frontier of Brazil and Argentina. Participated of the study 405 individuals living in the municipalities of Bandeirante, Santa Helena, Princesa and Tunapolis, state of Santa Catarina, Brazil. IgG antibodies to hantavirus were analyzed in sera by an ELISA that uses a recombinant N protein of Araraquara hantavirus as antigen. The results were also confirmed by immunofluorescent test. Eight individuals showed antibodies to hantavirus (1.97% positivity), with serum titers ranging from 100 to 800. Six seropositives were males, older than 30 years and farmers. Our results reinforce previous data on hantavirus circulation and human infections in the southern border of Brazil with Argentina.

Trombose coronariana como primeira complicação da aíndrome antifosfolípide

A síndrome do anticorpo antifosfolípide (SAF) é uma trombofilia autoimune, caracterizada pela presença de anticorpos plasmáticos contra fosfolípides, associada a episódios recorrentes de trombose venosa e/ou arterial e morbidade gestacional (especialmente abortamento de repetição). Reportamos o caso de uma paciente feminina, jovem, com diagnóstico de lúpus eritematoso sistêmico (LES), associado à presença de anticorpos antifosfolípide de longa data, com apresentação de infarto agudo do miocárdio (IAM) por trombose proximal da artéria descendente anterior como primeira complicação clínica da SAF.

Prevalência e fatores de risco de leptospirose bovina no Estado do Maranhão

Foram investigados a prevalência e os fatores de risco da leptospirose bovina no Estado do Maranhão. O Estado foi dividido em quatro circuitos amostrais com base em parâmetros de produção distintos que variam conforme os diferentes sistemas de produção, as práticas de manejo, a finalidade de exploração, o tamanho médio dos rebanhos e os sistemas de comercialização. Objetivou-se estudar as características epidemiológicas da leptospirose bovina no Estado do Maranhão, de modo a determinar a prevalência em bovinos e em rebanhos, detectar as sorovariedades de Leptospira spp. presentes, identificar os fatores de risco eventualmente associados à leptospirose em bovinos e diferenciar os circuitos pecuários entre si no que se refere à prevalência de leptospirose. A pesquisa foi realizada em 136 propriedades rurais pertencentes ao circuito I, no qual 841 fêmeas bovinas com idade igual ou superior a 24 meses foram analisadas; 238 do circuito II, com 2.582 fêmeas analisadas; 122 do circuito III, com 869 fêmeas analisadas; e 77 do circuito IV, com 540 fêmeas analisadas; no total, 573 propriedades e 4.832 fêmeas foram estudadas. A presença de anticorpos contra Leptospira spp. foi verificada pela técnica de soroaglutinação microscópica (SAM). Das 4.832 fêmeas bovinas analisadas, 1.904 (35,94%; IC 95% = 33,01% - 38,98%) foram reagentes. Das 573 propriedades analisadas, 380 (64,81%; IC 95% = 61,10% - 68,35%) foram consideradas positivas. As sorovariedades Hardjo e Wolffi foram as mais frequentes em todo o Estado. O circuito III foi o que apresentou menor prevalência de leptospirose em todas as comparações. As variáveis identificadas como fatores de risco de leptospirose foram: presença de equinos (p = 0,000), presença de capivaras (p = 0,034) e rebanhos bovinos com 32 ou mais fêmeas adultas (p = 0,002).

Fagocitose intensificada de Corynebacterium pseudotuberculosis por células da série monócito-macrófago de caprinos naturalmente infectados pelo vírus da artrite encefalite

A Artrite Encefalite Caprina (AEC) e a Linfadenite Caseosa (LC) possuem alta incidência e transmissibilidade em pequenos ruminantes. Como ambas possuem tropismo por monócitos-macrófagos e afetam mecanismos da resposta inata do hospedeiro, acredita-se que a AEC predispõe o animal a infecções por Corynebacteruim pseudotuberculosis, agente etiológico da LC. Para confirmar esta hipótese, avaliou-se a fagocitose de células da série monócito-macrófago de cabras naturalmente infectadas pelo vírus da AEC (VAEC). Para tanto, foram utilizadas 30 cabras da raça Saanen, alocadas em dois grupos distintos, com 15 animais cada, conforme a sororreatividade de anticorpos séricos antivírus da AEC. Células mononucleares de sangue periférico foram isoladas por gradiente de densidade e plaqueadas para isolamento de células da série monócito-macrófago. Posteriormente, o ensaio de fagocitose de C. pseudotuberculosis foi realizado, após incubação por duas horas a 37ºC a 5% de CO2, e a visualização da fagocitose foi identificada por microscopia óptica. O presente estudo não encontrou diferença na porcentagem de monócito-macrófagos que realizaram fagocitose entre os diferentes grupos (P = 0,41). Todavia, a análise quantitativa de bactérias fagocitadas, demonstrou maior capacidade fagocítica pelos macrófagos-monócitos do grupo sororreagente ao vírus da AEC. Correlação entre monócitos fagocitando e macrófagos que fagocitaram mais de 12 bactérias foi observado neste grupo (r = 0,488; P = 0,006), não sendo o mesmo encontrado no grupo de animais sorroreagentes negativos. Os dados demonstram aumento na intensidade da fagocitose de macrófagos de animais infectados com o vírus da AEC.

Serological, clinical and epidemiological evaluation of toxocariasis in urban areas of south Brazil.

Toxocariasis is a worldwide public-health problem that poses major risks to children who may accidentally ingest embryonated eggs of Toxocara. The objectives of this study were to investigate the occurrence of anti-Toxocara spp. antibodies in children and adolescents and the variables that may be involved, as well as environmental contamination by Toxocara spp. eggs, in urban recreation areas of north central mesoregion, Paraná State, Brazil. From June 2005 to March 2007. a total of 376 blood samples were collected by the Public Health Service from children and adolescents one to 12 years old, of both genders. Samples were analyzed by the indirect ELISA method for detection of anti-Toxocara antibodies. Serum samples were previously absorbed with Ascaris suum antigens, and considered positive with a reagent reactivity index ≥1. Soil samples from all of the public squares and schools located in the four evaluated municipalities that had sand surfaces (n = 19) or lawns (n = 15) were analyzed. Of the 376 serum samples, 194 (51.6%) were positive. The seroprevalence rate was substantially higher among children aging one to five years (p = 0.001) and six to eight years (p = 0.022). The clinical signs and symptoms investigated did not show a statistical difference between seropositive and seronegative individuals (p > 0.05). In 76.5% of the investigated recreation places, eggs of Toxocara were detected in at least one of the five collected samples. Recreation areas from public schools were 2.8 times more contaminated than from public squares. It is important to institute educational programs to inform families and educators, as well as to improve sanitary control of animals and cleaning of the areas intended for recreation in order to prevent toxocariasis.

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Experimental antiviral therapy against different rabies virus lineages using transfection with anti-rabies antibodies

Financial Support: FAPESP