TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients.

OBJECTIVE: To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. METHODS: One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. RESULTS: After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. CONCLUSION: This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644.

The dilemma of influenza vaccine recommendations when applied to the tropics: the Brazilian case examined under alternative scenarios.

Since 1999 the World Health Organization issues annually an additional influenza vaccine composition recommendation. This initiative aimed to extend to the Southern Hemisphere (SH) the benefits-previously enjoyed only by the Northern Hemisphere (NH)--of a vaccine recommendation issued as close as possible to the moment just before the onset of the influenza epidemic season. A short time between the issue of the recommendation and vaccine delivery is needed to maximize the chances of correct matching between putative circulating strains and one of the three strains present in the vaccine composition. Here we compare the effectiveness of the SH influenza vaccination adopted in Brazil with hypothetical alternative scenarios defined by different timings of vaccine delivery and/or composition. Scores were based on the temporal overlap between vaccine-induced protection and circulating strains. Viral data were obtained between 1999 and 2007 from constant surveillance and strain characterization in two Brazilian cities: Belém, located at the Equatorial region, and São Paulo, at the limit between the tropical and subtropical regions. Our results show that, among currently feasible options, the best strategy for Brazil would be to adopt the NH composition and timing, as in such case protection would increase from 30% to 65% (p<.01) if past data can be used as a prediction of the future. The influenza season starts in Brazil (and in the equator virtually ends) well before the SH winter, making the current delivery of the SH vaccination in April too late to be effective. Since Brazil encompasses a large area of the Southern Hemisphere, our results point to the possibility of these conclusions being similarly valid for other tropical regions.

[Adenovirus conjunctivitis diagnosis using RPS Adenodetector]. / Diagnóstico de conjuntivite adenoviral pelo RPS Adenodetector.

PURPOSE: To evaluate the RPS Adenodetector, a rapid immunochromatographic test, in the diagnosis of patients with clinical overt adenoviral conjunctivitis. METHODS: Consecutive case series. Patients underwent conjunctiva scraping for RPS Adenodetector test and culture to identify adenovirus. RESULTS: A total of 11 patients were studied, and 10 had unilateral disease. Five (45.5%) had symptoms for 2 days, 5 for three days, and 1 for 7 days. Adenovirus culture was positive in 8 patients (73%) and RPS Adenodetector was positive in 9 (82%) patients. Eight patients had adenovirus identification by both methods. In one patient the RPS Adenodetector was positive in contrast to a negative culture. The two patients revealing negative RPS Adenodetector results also had negative cultures. The sensitivity was 100% and the specificity was 67%. CONCLUSION: The RPS Adenodetector is a useful tool in the rapid diagnosis of adenovirus conjunctivitis and may contribute to the spread control of this highly contagious disease.

Diagnóstico de conjuntivite adenoviral pelo RPS Adenodetector® / Adenovirus conjunctivitis diagnosis using RPS Adenodetector®

OBJETIVO: Avaliar a utilização do RPS Adenodetector®, como método diagnóstico de pacientes com quadro clínico de conjuntivite adenoviral. MÉTODOS: Análise de série de casos consecutivos de pacientes com diagnóstico clínico de ceratoconjuntivite adenoviral submetidos comparativamente ao teste RPS Adenodetector® e a raspado conjuntival para cultura de vírus. RESULTADOS: Dos 11 pacientes avaliados, 10 pacientes apresentavam acometimento unilateral. Em relação ao tempo de início dos sintomas no momento da colheita, 5 (45,5 por cento) pacientes apresentavam dois dias de história, 5 (45,5 por cento) apresentavam três dias e 1 (9,1 por cento) apresentava 7 dias. A cultura para adenovírus foi positiva em 8 pacientes (73 por cento) e o RPS Adenodetector® foi positivo em 9 pacientes (82 por cento). Oito pacientes apresentaram o teste rápido e cultura positiva. Um paciente apresentou teste RPS Adenodetector® positivo com cultura negativa. Os dois pacientes com teste RPS Adenodetector® negativo apresentaram cultura negativa. O RPS Adenodetector® mostrou sensibilidade de 100 por cento e especificidade de 67 por cento adotando-se a cultura de vírus como exame padrão-ouro para o diagnóstico de conjuntivite adenoviral. CONCLUSÃO: O RPS Adenodetector® foi útil para o diagnóstico de conjuntivite adenoviral e pode auxiliar na orientação do paciente quanto ao contágio e disseminação da doença.

PURPOSE: To evaluate the RPS Adenodetector®, a rapid immunochromatographic test, in the diagnosis of patients with clinical overt adenoviral conjunctivitis. METHODS: Consecutive case series. Patients underwent conjunctiva scraping for RPS Adenodetector® test and culture to identify adenovirus. RESULTS: A total of 11 patients were studied, and 10 had unilateral disease. Five (45.5 percent) had symptoms for 2 days, 5 for three days, and 1 for 7 days. Adenovirus culture was positive in 8 patients (73 percent) and RPS Adenodetector® was positive in 9 (82 percent) patients. Eight patients had adenovirus identification by both methods. In one patient the RPS Adenodetector® was positive in contrast to a negative culture. The two patients revealing negative RPS Adenodetector® results also had negative cultures. The sensitivity was 100 percent and the specificity was 67 percent. CONCLUSION: The RPS Adenodetector® is a useful tool in the rapid diagnosis of adenovirus conjunctivitis and may contribute to the spread control of this highly contagious disease.

Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation.

The objectives of this study were to determine the incidence of infection by respiratory viruses in preterm infants submitted to mechanical ventilation, and to evaluate the clinical, laboratory and radiological patterns of viral infections among hospitalized infants in the neonatal intensive care unit (NICU) with any kind of acute respiratory failure. Seventy-eight preterm infants were studied from November 2000 to September 2002. The newborns were classified into two groups: with viral infection (Group I) and without viral infection (Group II). Respiratory viruses were diagnosed in 23 preterm infants (29.5%); the most frequent was respiratory syncytial virus (RSV) (14.1%), followed by influenza A virus (10.2%). Rhinorrhea, wheezing, vomiting and diarrhea, pneumonia, atelectasis, and interstitial infiltrate were significantly more frequent in newborns with nosocomial viral infection. There was a correlation between nosocomial viral infection and low values of C-reactive protein. Two patients with mixed infection from Group I died during the hospital stay. In conclusion, RSV was the most frequent virus in these patients. It was observed that, although the majority of viral lower respiratory tract infections had a favorable course, some patients presented a serious and prolonged clinical manifestation, especially when there was concomitant bacterial or fungal infection.

Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation

Os objetivos do estudo foram determinar a incidência de infecção por vírus respiratórios em crianças pré-termo externas submetidas à ventilação mecânica e avaliar os padrões clínico, laboratorial e radiológico das infecções virais entre crianças pré-termo internadas em unidade de cuidados intensivos neonatal (NICU) com insuficiência respiratória aguda de qualquer tipo. Setenta e oito crianças pré-termo externas foram estudadas de Novembro de 2000 a Setembro de 2002. Os recém-nascidos foram classificados em dois grupos: com infecção viral (Grupo I) e sem infecção viral (Grupo II). Vírus respiratórios foram diagnosticados em 23 crianças pré-termo (29,5%); o vírus mais importante foi o sincicial respiratório (VSR) (14,1%), seguido pelo vírus influenza A (10,2%). Rinorréia, sibilância, vômitos e diarréia, pneumonia, atelectasia e infiltrado intersticial foram significativamente mais freqüentes nos recém-nascidos com infecção viral hospitalar. Houve correlação entre infecção viral hospitalar e valores baixos de proteína C-reativa. Dois pacientes com infecção mista do Grupo I faleceram durante a internação. Em conclusão, o VSR foi vírus mais incidente nestes pacientes com infecção nosocomial do trato respiratório inferior. Foi observado que, embora a maioria das infecções respiratórias virais tenham tido uma evolução favorável, alguns pacientes apresentaram quadro clínico grave e prolongado, principalmente quando houve infecção bacteriana ou fúngica concomitante.

Occurrence of influenza B/Hong Kong-like strains in Brazil, during 2002.

Through the influenza virus surveillance from January to October 2002, influenza B/Hong Kong-like strains circulating in the Southeast and Centre East regions of Brazil have been demonstrated. This strain is a variant from B/Victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to South-Eastern Asia. A total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the Southeast and Centre East regions of Brazil, of which 86 (17.13%) were positive for influenza virus. Among them 12 (13.95%) were characterized as B/Hong Kong/330/2001; 3 (3.49%) as B/Hong Kong/1351/2002 a variant from B/Hong Kong/330/2001; 1 (1.16%) as B/Sichuan/379/99; 1 (1.16%) as B/Shizuoka/5/2001, until now. The percentages of cases notified during the surveillance period were 34.88%, 15.12%, 15.12%, 4.65%, 15.12%, 13.95%, in the age groups of 0-4, 5-10, 11-15, 16-20, 21-30, 31-50, respectively. The highest proportion of isolates was observed among children younger than 4 years but serious morbidity and mortality has not been observed among people older than 65 years, although B influenza virus component for vaccination campaign 2002 was B/Sichuan/379/99 strain. This was probably due to the elderly protection acquired against B/Victoria/02/88. In addition, in influenza A/Panama/2007/99-like (H3N2) strains 22 (25.58%) were also detected, but influenza A(H1N1) has not been detected yet.

Occurrence of influenza B/Hong Kong-Like strains in Brazil, during 2002

Through the influenza virus surveillance from January to October 2002, influenza B/Hong Kong-like strains circulating in the Southeast and Centre East regions of Brazil have been demonstrated. This strain is a variant from B/Victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to South-Eastern Asia. A total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the Southeast and Centre East regions of Brazil, of which 86 (17.13 percent) were positive for influenza virus. Among them 12 (13.95 percent) were characterized as B/Hong Kong/330/2001; 3 (3.49 percent) as B/Hong Kong/1351/2002 a variant from B/Hong Kong/330/2001; 1 (1.16 percent) as B/Sichuan/379/99; 1 (1.16 percent) as B/Shizuoka/5/2001, until now. The percentages of cases notified during the surveillance period were 34.88 percent, 15.12 percent, 15.12 percent, 4.65 percent, 15.12 percent, 13.95 percent, in the age groups of 0-4, 5-10, 11-15, 16-20, 21-30, 31-50, respectively. The highest proportion of isolates was observed among children younger than 4 years but serious morbidity and mortality has not been observed among people older than 65 years, although B influenza virus component for vaccination campaign 2002 was B/Sichuan/379/99 strain. This was probably due to the elderly protection acquired against B/Victoria/02/88. In addition, in influenza A/Panama/2007/99-like (H3N2) strains 22 (25.58 percent) were also detected, but influenza A(H1N1) has not been detected yet

Outbreak of influenza type A (H1N1) in Iporanga, Säo Paulo State, Brazil

From June to July 1999 an outbreak of acute respiratory illness occurred in the town of Iporanga. Out of a total of 4,837 inhabitants, 324 cases were notified to the Regional Surveillance Service. Influenza virus was isolated from 57.1 percent of the collected samples and 100 percent seroconversion to influenza A (H1N1) was obtained in 20 paired sera tested. The isolates were related to the A/Bayern/07/95 strain (H1N1). The percentages of cases notified during the outbreak were 28.4 percent, 29.0 percent, 20.7 percent, 6.2 percent and 15.7 percent in the age groups of 0-4, 5-9, 10-14, 15-19 and older than 20 years, respectively. The highest proportion of positives was observed among children younger than 14 years and no cases were notified in people older than 65 years, none of whom had been recently vaccinated against influenza. These findings suggest a significant vaccine protection against A/Bayern/7/95, the H1 component included in the 1997-98 influenza vaccine for elderly people. This viral strain is antigenically and genetically related to A/Beijing/262/95, the H1 component of the 1999 vaccine. Vaccines containing A/Beijing/262/95 (H1N1) stimulated post-immunization hemagglutination inhibition antibodies equivalent in frequency and titre to both A/Beijing/262/95-like and A/Bayern/7/95-like viruses. Thus, this investigation demonstrates the effectiveness of vaccination against influenza virus in the elderly

Comparative study of adenoviruses with monoclonal antibodies

The obtainment of monoclonal antibodies for adenovirus species 4(Ad4) is described. The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme-Linked Immunosorbent Assay (ELISA), in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C), 4 (subgenus E), 7 and 16 (subgenus B) and 9 (subgenus D). Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII) and one monoclonal antibody that cross reacted with adenovirus species 4 and 7 (2HIII) were obtained.

Enterovírus-70 na regiäo metropolitana de Säo Paulo, Brasil, de l984 a1987: aspectos da infecçäo em períodos epidêmicos e endêmico / Enterovirus 70 in the metropolitan region of Säo Paulo, Brazil, from 1984 to 1987: infection aspects in endemic and epidemic periods

Säo apresentados os resultados dos estudos sobre o comportamento do Enterovirus-70 (EV-70) na regiäo metropolitana de Säo Paulo desde sua provável introduçäo no veräo de 1984, determinando extensa de conjuntivite hemorrágica aguda (C.H.A.), até o final de 1987 abrangendo preríodo em que este agravo foi pouco notado. Na fase epidêmica ocorrida no primeiro trimestre de 1984 foram estudados 291 indivíduos divididos em três grupos denominados A, B e C, o primeiro formado por pessoas atingidas pela C.H.A. e os outros dois por indivíduos näo atingidos por este agravo mas que, respectivamente, referiam contato domiciliar com casos de C.H.A. e os que näo referiam o citado contato. A demonstraçäo de anticorpos se fez pela técnica de imunofluorescência (IFI) para detectar IgM específico para EV-70 e pela prova de neutralizaçäo em cultura de células BHK-21. Verificou-se que 56,7%,33,3%e 20,6% dos indivíduos pertencentes, respectivamente, aos grupos A,B e C apresentavam anticorpos específicos da classe IgM. No grupo A a faixa etária mais atingida foi a de 10 a 29 anos. No período que vai do fim da primeira e única epidemia até o final de 1987, identificaram-se três casos esporádicos de C.H.A. e 10 pacientes com afecçäo neurológica aguda associada à infecçäo recente pelo EV-70. Nove, destes 10 casos, apresentaram paralisia de nervos cranianos, todos evoluindo sem sequelas clinicamente discerníveis. As formas assintomáticas e os casos esporádicos de C.H.A. e de afecçoes neurológicas mantiveram a circulaçäo do EV-70 no período epidêmico

Enzyme linked immunosorbent assay: determination of anti-adenovirus antibodies in an infant population

Com a finalidade de encontrar um ensaio preciso para a detecçäo de anticorpos anti-adenovírus, o teste ELISA recentemente padronizado foi compardo à inmunofluorescência indireta (IFI) e à fixaçäo de complemento (FC). Após testar 58 sóros, o ELISA demonstrou maior sensibilidade do que a IFI e a FC, que mostraram sensibilidades relativas de 94% e 63%, respectivamente. A falta de um padräo universal näo permitiu alcançar conclusöes definitivas quanto à especificidade dos ensaios. Além disso, o ELISA foi utilizado para estabelecer a prevalência de anticorpos anti-adenovírus em 116 crianças entre 1 e 24 meses de idade (média 7.28). Os dados mostraram que os anticorpos maternos desaparecem ao redor dos 5 a 6 meses de idade e que mais de 80% das crianças tinham sido infectadas antes dos 10 meses de idade

Investigaçäo etiológica em casos de conjuntivite hemorrágica aguda em regiöes do Estado de Säo Paulo, Brasil, 1984 / Etiologic study of acute haemorrhagic conjunctivitis in regions of Säo Paulo State, Brasil, 1984

Nos meses de janeiro a março de 1983 e de 1984 ocorreram sucessivamente duas epidemias de conjuntivite hemorrágica aguda (C.H.A.) no Estado de Säo Paulo, a primeira atingindo exclusivamente a área litorânea e a segunda, mais extensa, abrangendo também regiöes do planalto. A presente investigaçäo apresenta dados sobre aspectos etiológicos da epidemia de C.A.H. ocorrida em 1984. Foram examinadas amostras pareadas de soro de 73 pacientes para a pesquisa de anticorpos e amostras da secreçäo conjuntival de 179 casos com C.H.A., para a tentativa de isolamento de vírus provenientes de diferentes regiöes do Estado de Säo Paulo. Houve conversäo sorológica em 45,2% dos 73 pacientes examinados e presença de anticorpos específicos para EV-70 sem conversäo sorológica em outros 19,2%. As proporçöes mais elevadas de casos positivos situaram-se entre pacientes maiores de 20 anos, com taxas de 70,6% para o grupo etário de 20 a 29 anos, de 55,6% na faixa de 30 a 39 anos e de 72,7% em maiores de 40 anos. Foram isoladas de amostras de secreçäo conjuntival 7 cepas de adenovírus, 1 de herpes simples e 1 de EV-70. Nenhum dos soros pareados examinados foi positivo para adenovirus e, nos casos em que esses vírus foram isolados, näo foi possível obter soros pareados para a comprovaçäo sorológica de infecçäo. Os resultados obtidos confirmam a participaçäo de EV-70 nessa epidemia. Näo foram identificadas complicaçöes neurológicas associadas à infecçäo pelo EV-70

Frequência de anticorpos para os vírus da influenza tipos A e B, em habitantes da cidade de São Paulo, Brasil, em 1982 / Frequency of antibodies against type A and B influenza virus in inhabitants of the city of Säo Paulo, Brazil, in 1982

Em fevereiro de 1982, foram colhidos 180 soros de 180 habitantes da cidade de São Paulo, de diferentes grupos etários, e realizadas titulaçôes de anticorpos inibi dores da hemaglutinação para os vírus da influenza tipos A e B. Os resultados obtidos com a estirpe A/Swine/Iowa/15/30 (H,N 1) em pessoas do grupo etário acima de 60 anos, e A/PR/8/34 (H,N ,), no grupo etário de 40 a 49 anos, revelaram percentagem elevada de soros positivos, determinados por infecção primária anterior por estes vírus ou variantes. Nos resultados obtidos com a estirpe A/Kumamoto/37/79 (H1N,), a elevada percentagem de soros positivos foi observada em habitantes dos grupos etários de 10 a 19 anos e 40 a 49 anos, indicando que cada grupo sofreu infecção primária pelo subtipo H,N 1 em 1977 e de 1947 a 1957, respectivamente. O vírus antigenicamente relacionado ao subtipo H,N. não circulou na população estudada desde a sua última pandemia ocorrida em 1957. Quanto à positividade de soros para os subtipos H3N21 A/Bangkok/1!79 (H3 N.) e A/Shiga/114/82 (H3 N.) esta se deveu provavelmente às reações cruzadas entre as variantes antigênicas desse subtipo (H,N.). A variante de influenza antigenicamente relacionada a B/Shiga/1/71 e B/Kanagawa/3/76 circulou em São Paulo nestes últimos anos. Porém, os resultados obtidos com a estirpe B/Shiga/75/81 demonstraram percentagens de soros positivos e médias geométricas baixas, significando que nenhuma variante relacionada a essa estirpe, até o momento, circulou nesta população (AU).

Anticorpos neutralizantes para adenovírus tipos 1 a 7 em habitantes da cidade de São Paulo, Brasil, em 1982 / Neutralizing antibodies for types 1 to 7 adenovirus in habitants of the city of Säo Paulo, Brazil

Foram pesquisados anticorpos neutralizantes para adenovírus tipos 1 a 7, em 180 soros de 180 indivíduos residentes na cidade de São Paulo, de diferentes grupos etários, colhidos em fevereiro de 1982. Os resultados mostraram que 53,3% dos doadores possuíam anticorpos para os tipos 1, 2, 3 e 5; 88,9% a 100% de indivíduos, com mais de 5 anos de idade, tinham anticorpos para adenovírus tipos 1 e 2. Quanto ao tipo 3 e 5, verificou-se elevação gradual, grupo a grupo, com percentagem um pouco menor que a dos tipos 1 e 2; porém, 71,9% a 92,8% dos indivíduos acima de 20 anos, possuíam anticorpos para os tipos 3 e 5. Em relação aos tipos 4 e 6, nas faixas etárias acima de 5 anos, a média foi de 50% "', para o tipo 7, aproximadamente de 20%. Foi verificado que 40% das crianças do grupo etário de O a 4 anos, não possuíam anticorpos para os 7 tipos de adenovírus estudados, e que 72,8% dos indivíduos acima de 10 anos possuíam anticorpos para 4-6 tipos diferentes de adenovírus (AU).