Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

ABSTRACT Introduction Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

Fatal Human herpesvirus 1 (HHV-1) infection in captive marmosets (Callithrix jacchus and Callithrix penicillata) in Brazil: clinical and pathological characterization / Infecção fatal por Herpesvirus simplex Tipo 1 (HHV-1) em saguis de cativeiro (Callithrix jacchus and Callithrix penicillata) no Brasil: caracterização clínica e patológica

Fatal Human herpesvirus 1 (HHV-1) was diagnosed in 12 captive marmosets (Callithrix jacchus and Callithrix penicillata) from metropolitan region of São Paulo, São Paulo State. Clinical signs were variable among the cases, but most affected marmosets presented signs associated with viral epithelial replication: oral, lingual and facial skin ulcers and hypersalivation, and viral replication in the central nervous system: prostration, seizure and aggressive behavior. Consistent microscopic findings were diffuse mild to severe nonsuppurative necrotizing meningoencephalitis with gliosis, vasculitis and neuronal necrosis. Additionally, in the brain, oral cavity, skin, adrenal gland and myoenteric plexus intranuclear inclusion bodies were present. Immunohistochemistry confirmed the presence of the HHV-1 antigen in association with lesions in the brain, oral and lingual mucosa, facial skin, adrenal gland and myoenteric plexus. HHV-1-specific polymerase chain reaction (PCR) analysis of the brain was carried out and the virus was detected in 7/8 infected marmosets. It is concluded that HHV-1 causes widespread fatal infection in marmosets.(AU)

Infecção fatal por Herpesvirus simplex Tipo 1 (HHV-1) foi diagnosticada em 12 saguis de cativeiro (Callithrix jacchus e Callithrix penicillata) provenientes da região metropolitana de São Paulo, Estado de São Paulo. Os sinais clínicos foram variáveis entres os casos, no entanto, a maioria dos saguis afetados apresentavam sinais associados à replicação viral em epitélios: úlceras na cavidade oral, língua e pele da face e hipersalivação; e no sistema nervoso central: prostração, convulsão e comportamento agressivo. Histologicamente, o principal achado foi meningoencefalite necrosante não supurativa difusa, leve a acentuada com gliose, vasculite e necrose neuronal. Inclusões intranucleares também foram observadas em encéfalo, cavidade oral, pele, glândula adrenal e plexo mioentérico. A imuno-histoquímica anti-HHV-1 confirmou a presença do antígeno viral em associação às lesões em encéfalo, mucosa oral e lingual, pele da face, glândula adrenal e plexo mioentérico. Em 7/8 saguis infectados foi detectada a presença de HHV-1 por reação em cadeia da polimerase (PCR) a partir de amostras de encéfalo. Conclui-se que HHV-1 causa uma infecção disseminada e fatal em saguis.(AU)

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

INTRODUCTION: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PMl). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. MATERIAL AND METHODS: This was a retrospective study of HIV-infected patients admitted consecutively for JCVassociated CNS diseases in a referral teaching center in São Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PMl; 2) inflammatory PMl; and 3) JC virus granule cell neuronopathy (GCN). RESULTS: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PMl: 42 (89%); 2) inflammatory PMl: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. overall mortality during hospitalization was 34%. CONCLUSIONS: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature / Complicações neurológicas causadas pelo citomegalovírus em pacientes com AIDS: estudo retrospectivo de 13 casos e revisão da literatura

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69 percent) were men. At admission all patients were aware of their HIV status and only four (31 percent) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62 percent) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62 percent), polyradiculopathy (n = 7; 54 percent), focal encephalitis (rhombencephalitis) (n = 1; 8 percent), and ventriculo-encephalitis (n = 1; 8 percent). Seven (54 percent) patients presented extra-neural CMV disease and four (31 percent) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38 percent. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50 percent) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20 percent). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

As complicações neurológicas causadas pelo Citomegalovírus (CMV) em pacientes com aids são raramente relatadas na era HAART. O objetivo deste estudo foi descrever as principais características clínicas e laboratoriais de pacientes com complicações neurológicas associadas ao CMV em pacientes com aids admitidos em centro de referência em Sao Paulo, Brasil. A doença citomegálica precisou da identificação do vírus no líquor mediante a reação em cadeia da polimerase (PCR). Treze casos foram identificados entre janeiro de 2004 e dezembro de 2008. A mediana da idade foi 38 anos e nove (69 por cento) eram homens. Na admissão, todos os pacientes sabiam do seu status sorológico para o HIV e apenas quatro (31 por cento) pacientes usavam HAART. A doença citomegálica foi a primeira doença definidora de aids em oito (62 por cento) pacientes. As síndromes neurológicas identificadas foram: encefalite difusa (n = 7; 62 por cento), polirradiculopatia (n = 7; 54 por cento), encefalite focal (romboencefalite) (n = 1; 8 por cento), e ventrículo-encefalite (n = 1; 8 por cento). Sete (54 por cento) pacientes apresentaram doença citomegálica fora do sistema nervoso e quatro (31 por cento) tiveram retinite. A mediana da contagem de células CD4+ foi 13 células/µL. A mortalidade global durante a internação foi 38 por cento. Oito pacientes usaram ganciclovir ou foscarnet (mortalidade: 50 por cento) e cinco pacientes usaram ganciclovir e foscarnet (mortalidade: 20 por cento). Nenhum paciente apresentou critérios diagnósticos da síndrome inflamatória de reconstituição imunológica. Quatro pacientes foram perdidos do acompanhamento ambulatorial e três pacientes apresentaram reconstituição imunológica e descontinuaram as profilaxias secundárias. Embora raras, as particulares síndromes neurológicas causadas pelo CMV continuam causando elevada mortalidade em pacientes com aids. A sobrevida depende do uso de terapia antiviral efetiva contra o CMV e a introdução oportuna do HAART.

Aids-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil / Leucoencefalopatia multifocal progressiva em pacientes com aids: estudo retrospectivo em um centro de referência de São Paulo, Brasil

Few data are available about progressive multifocal leukoencephalopathy (PML) in patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The objectives of this study were to describe the main features of patients with PML and estimate its frequency among AIDS patients with central nervous system (CNS) opportunistic diseases admitted to the Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive study was performed. Twelve (6 percent) cases of PML were identified among 219 patients with neurological diseases. The median age of patients with PML was 36 years and nine (75 percent) were men. Nine (75 percent) patients were not on antiretroviral therapy at admission. The most common clinical manifestations were: focal weakness (75 percent), speech disturbances (58 percent), visual disturbances (42 percent), cognitive dysfunction (42 percent), and impaired coordination (42 percent). The median CD4+ T-cell count was 45 cells/µL. Eight (67 percent) of 12 patients were laboratory-confirmed with PML and four (33 percent) were possible cases. Eleven (92 percent) presented classic PML and only one case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four (33 percent) patients, PML was the first AIDS-defining illness. During hospitalization, three patients (25 percent) died as a result of nosocomial pneumonia and nine (75 percent) were discharged to home. Cases of PML were only exceeded by cases of cerebral toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three more frequent neurologic opportunistic infections in Brazil. The results of this study suggest that PML is not an uncommon HIV-related neurologic disorder in a referral center in Brazil.

Existe informação limitada sobre a presença da leucoencefalopatia multifocal progressiva (LEMP) em pacientes com aids no Brasil. Os objetivos do presente estudo foram descrever as principais características dos pacientes com LEMP e estimar a freqüência desta doença em pacientes com aids e doenças oportunistas do sistema nervoso central (SNC) internados em um centro de referência de São Paulo, Brasil. Neste estudo retrospectivo e descritivo, identificamos 12 (6 por cento) casos de LEMP entre 219 pacientes com doenças neurológicas oportunistas do SNC. A idade média dos pacientes com LEMP foi 36 anos e 9 (75 por cento) eram do sexo masculino. As manifestações clínicas mais freqüentes foram: déficits focais (75 por cento), alterações da fala (58 por cento), alterações visuais (42 por cento), alterações cognitivas (42 por cento), e problemas de coordenação (42 por cento). A média da contagem de células T-CD4+ foi 45 células/µL. Oito (67 por cento) dos 12 pacientes com LEMP tiveram diagnóstico confirmado laboratorialmente e em quatro (33 por cento) casos o diagnóstico foi possível. Onze (92 por cento) pacientes apresentaram LEMP clássica e um caso teve LEMP associada à síndrome de reconstituição imune. Em quatro (33 por cento) pacientes, a LEMP foi a primeira doença definidora de aids. Durante a internação, três pacientes (25 por cento) faleceram devido a pneumonia hospitalar e nove (75 por cento) tiveram alta. A LEMP foi apenas ultrapassada em freqüência pela toxoplasmose cerebral, a meningoencefalite criptococócica e a neurotuberculose, as três mais freqüentes doenças neurológicas oportunistas no Brasil. Os resultados deste estudo sugerem que a LEMP não é uma complicação neurológica incomum em pacientes com infecção pelo HIV no nosso meio.

Aetiology and clinical presentation of pneumonia in hospitalized and outpatient children in Northeast Brazil and risk factors for severity.

Data on presentation, aetiology, and prognostic indicators of childhood pneumonia, which can help design strategies for controlling the disease, are generally scarce in developing countries. In this paper, the distribution of aetiologic agents, clinical presentation, and evolution of pneumonia cases are described, and the factors associated with duration of pneumonia episode and of hospital admission examined. During June 1994-June 1995, 472 children, aged 6-59 months, with clinical diagnosis of pneumonia, who were admitted to hospital or treated as outpatients, were investigated in Recife, Northeast Brazil. Pneumonia, in most cases, was confirmed by radiology. A combination of methods was used for investigating the aetiology of pneumonia. Data obtained on a large number of clinical, socioeconomic and biological variables were analyzed to determine the prognostic factors for the severity and outcome of pneumonia. Bacteria were identified in 26.7% of the cases, while viruses and mixed infections accounted for 8.4% and 2.7% respectively. Haemophilus influenzae (18.9%), Streptococcus pneumoniae (6.4%), and respiratory syncytial virus (5.0%) were most often identified. The pneumonia case-fatality rate was 0.8%. The best clinical predictors of severity were: lung complications at baseline, tachypnoea (for duration of episode), and chest indrawing (for duration of hospital admission). Young age, low birth-weight, and prolonged fever prior to admission to the study also predicted a more prolonged illness, and under-nutrition was a predictor of longer hospital stay. While the development of new vaccines is an important measure for reducing morbidity and mortality due to pneumonia, emphasis on appropriate case management needs to be maintained, with particular attention to children who show the identified risk factors for a poor prognosis.

Hepatitis B vaccine in infants: a randomized controlled trial comparing gluteal versus anterolateral thigh muscle administration

A significantly diminished antibody response to hepatitis B vaccine has been demonstrated in adults when the buttock is used as the injection site. However, in Brazil, the buttock continues to be recommended as site of injection for intramuscular administration of vaccines in infants. In this age group, there are no controlled studies evaluating the immunogenicity of the hepatitis B vaccine when administered at this site. In the present study, 258 infants were randomized to receive the hepatitis B vaccine either in the buttock (n = 123) or in the anterolateral thigh muscle (n = 135). The immunization schedule consisted of three doses of hepatitis B vaccine (Engerix Bâ, 10 mug) at 2, 4 and 9 months of age. There were no significant differences in the proportion of seroconversion (99.3 percent x 99.2 percent), or in the geometric mean titer of ELISA anti-HBs (1,862.1 x 1,229.0 mIU/mL) between the two groups. This study demonstrates that a satisfactory serological response can be obtained when the hepatitis B vaccine is administered intramuscularly into the buttock

Diagnósticos alternativos em pacientes com suspeita de encefalite por Herpes simplex e negativos à reaçäo em cadeia por polimerase (PCR) / Alternative diagnoses among suspected Herpes simplex encephalitis patients with negative polymerase chain reaction (PCR)

O objetivo do presente estudo é analisar os diagnósticos encontrados em uma série de pacientes cuja suspeita clínica inicial era de encefalite herpética (HSE), mas que tiveram este diagnóstico afastado através de resultado negativo à reaçäo em cadeia por polimerase (PCR) para detecçäo do Herpes simples (HSV) em líquido cefalorraqueano (LCR). Em 43 dos 61 pacientes com suspeita de HSE estudados (70,5 por cento) o resultado à PCR foi negativo. O diagnóstico diferencial foi elucidado em 41,9 por cento dos 43 casos em que a PCR para HSV resultou negativa. Nestes, as patologias diagnosticadas foram infecçöes virais (2 casos-11,1 por cento) e näo virais (5 casos-27,2 por cento), doenças vasculares (4 casos-22,2 por cento), desmielinizantes (3 casos-16,7 por cento), distúrbios tóxico-metabólicos (3 casos-16,7 por cento) e tumor do sistema nervoso central (1 caso-5,6 por cento). A pouca especificidade do quadro clínico e a disponibilidade de tratamento eficaz e seguro para a HSE justificam a grande quantidade de casos tratados com aciclovir, mas cujo diagnóstico de encefalite pelo HSV näo foi confirmado. A utilizaçäo da PCR no LCR contribuiu para melhor avaliaçäo etiológica dos quadros de encefalite aguda aqui estudados

Cytomegalovirus infection in children with Down syndrome in a day-care center in Brazil

This study evaluates the transmission of CMV infection in 120 children aged 1 to 15 years with Down syndrome who attended a day-care center for handicapped children in São Paulo, Brazil. A blood sample was obtained from each children at the beginning of the study for detection of IgG and IgM cytomegalovirus (CMV) antibodies by an immunofluorescence assay. Samples of saliva and urine were obtained every 3 months from the children with CMV antibodies to detect shedding of the virus by culture in human foreskin fibroblasts, by detection of pp65 CMV-antigen and by a nested PCR assay. The prevalence of anti CMV-IgG antibodies was 76.6 per cent (92/120), and IgM anti-CMV antibodies were detected in 13 per cent (12/92) of the seropositive children. During the first viral evaluation, CMV was detected in the urine and/or saliva in 39/90 (43.3 per cent) of the seropositive children. In the second and third evaluations, CMV was detected in 41/89 (46 per cent) and in 35/89 (39.3 per cent) children, respectively. Detection of CMV was shown both in urine and saliva in 28/39 (71.8 per cnet), 19/41(46.3 per cent) and 20/35 (57.1 per cent) of the children excreting the virus, respectively...

Cytomegalovirus infection in a day-care center in the municipality of São Paulo

The prevalence of antibodies against cytomegalovirus (CMV) and the incidence of CMV infection were tested in 98 children aged 5 to 36 months who attended the day-care center of a University hospital in São Paulo. At the beginning of the study the overall prevalence of anti-CMV IgG antibodies was 44 (43/98). Saliva and/or urine samples were obtained from 38 of the 43 children that were seropositive at the beginning of the study for isolation of the virus, and 52.6 of these children were found to excrete CMV in one of the two materials. Among the 37 children that were initially seronegative from whom it was possible to obtain a new blood sample 6 to 12 months later, 22 (59.5) presented seroconversion. The rate of viral excretion through urine or saliva from the children that seroconverted was 50. These results indicate that CMV infection is frequent and occurs early among the children who attend this day-care center. However, controlled studies using molecular epidemiology techniques are needed to define more precisely the role of day-care centers in CMV dissemination.

Avaliaçäo sorológica de imunizaçäo contra o sarampo com duas doses administradas aos 6 e 11 meses de idade: estudo prospectivo / Serological evaluation of the immunization against meales with 2 doses administered at 6 and 11 months of age: a prospective study

A eficácia sorológica de um esquema de vacinaçäo contra o sarampo empregando duas doses da vacina BIKEN CAM 70, sendo a primeira dose administrada aos 6 meses de idade e a segunda aos 11 meses de idade foi avaliada através de um estudo prospectivo. A amostra de sangue foi colhida entre 6 e 12 meses (média de 8,0 ñ 1,7 meses) após a segunda dose da vacina, tendo-se empregado para pesquisa de anticorpos específicos a reaçäo de imunofluorescência indireta (RIFI) e a técnica imunoenzimática ELISA. Anticorpos para o sarampo na amostra de sangue pós-vacinal foram detectados em 88,5% (85/96) das crianças quando foi empregada a RIFI e em 96,8% (93/96) quando se empregou a técnica imunoenzimática ELISA. Nenhuma das crianças apresentou, durante o perído do estudo, quadro clínico compatível com sarampo. Em regiöes em que uma proporçäo significativa de casos ocorrem antes s 9 meses de idade, o esquema de vacinaçäo de 2 doses, a primeira aos 6 e a segunda aos 11 meses de idade, pode representar alternativa válida para o controle do sarampo

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients

De janeiro de 1988 a janeiro de 1989 todos os pacients submetidos a transplante de coraçiao de medula óssea no Instituto do Coraçäo do Hospital das Clínicas da Faculdade de Medicina da Universidade de Siao Paulo foram estudados quanto à incidência e morbidade das infecçöes pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV) antes do transplantee 80% desenvolveram uma ou mais recorrências durante o período de observaçäo. Dos 12 episódios de infecçäo por CMV detectados neste estudo, 83% foram acompanhados por alteraçöes clínicas ou laboratoriais. Apenas um caso apresentou doença grave. A incidência de infecçöes causadas por vírus Herpes simplex (HSV) fossem reprsentadas por lesöes orais ou genitais, houve também umcaso de hepatite por HSV. Um dos 6 episódios de infecçäo, por HSV. Um dos 6 episódios de infecçäo, por HSV que foram tratados com aciclovir näo respondeu ao tratamento. Posteriormente, o paciente se beneficiou com o uso de ganciclovir. Todos os indivíduos apresentavam antes do transplante anticorpos anti-vírus da varicela zoster. Porém, näo houve nenhum caso de reativaçäo. Este estudo realça a importância do cocntrole diagnóstico ativo da infeccöes por herpes-vírus em pacientes transplantados. Tanto as infecçöes causadas por CMV como por HSV mostraram alta incidência e grande mortalidade indicando a necessidade de quimioprofilaxia