Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases

This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

Detection and genotyping of human adenovirus and sapovirus in children with acute gastroenteritis in Belém, Pará, between 1990 and 1992: first detection of GI. 7 and GV. 2 sapoviruses in Brazil

Abstract INTRODUCTION: Acute gastroenteritis (AGE) is one of the most common causes of morbidity and mortality, especially among children from developing countries. Human adenovirus (HAdV) and sapovirus (SaV) are among the agents that cause AGE. The present study aimed to detect and genotype HAdV and SaV in 172 fecal samples from children with AGE, collected during a surveillance study carried out in a low-income community in Belém, Pará, between 1990 and 1992. METHODS: HAdV was detected by nested PCR, using primers Hex1deg/Hex2deg and NeHex3deg/NeHex4deg. SaV was assayed by reverse transcription PCR (RT-PCR), nested PCR, and quantitative PCR. The nucleotide sequence was determined by direct cycle sequencing. RESULTS: Overall, 43% (74/172) of samples were positive for HAdV, of which 70.3% (52/74) were sequenced and classified as belonging to five different species, mostly A and F. For SaV, positivity was 5.2% (9/172) and genotypes GI.1, GI.7, GII.1, and GV.2 were detected. CONCLUSIONS: The present results reinforce the need for further studies to obtain epidemiological data about the circulation of these viruses in Brazil, especially in the Amazon Region, where data from the early 1990's are scarce. Furthermore, the study describes for the first time the detection of SaV genotypes GI.7 and GV.2 in Brazil, showing that these types circulated in the region more than 25 years ago.

Caliciviruses in hospitalized children, São Luís, Maranhão, 1997-1999: detection of norovirus GII. 12

ABSTRACT Gastroenteritis is one of the most common diseases during childhood, with norovirus (NoV) and sapovirus (SaV) being two of its main causes. This study reports for the first time the incidence of these viruses in hospitalized children with and without gastroenteritis in São Luís, Maranhão. A total of 136 fecal samples were tested by enzyme immunoassays (EIA) for the detection of NoV and by reverse transcription-polymerase chain reaction (RT-PCR) for detection of both NoV and SaV. Positive samples for both agents were subjected to sequencing. The overall frequency of NoV as detected by EIA and RT-PCR was 17.6% (24/136) and 32.6% (15/46), respectively in diarrheic patients and 10.0% (9/90) in non-diarrheic patients (p < 0.01). Of the diarrheic patients, 17% had fever, vomiting and anorexia, and 13% developed fever, vomiting and abdominal pain. Of the 24 NoV-positive samples, 50% (12/24) were sequenced and classified as genotypes GII.3 (n = 1), GII.4 (6), GII.5 (1), GII.7 (2), GII.12 (1) and GII.16 (1). SaV frequency was 9.8% (11/112), with 22.6% (7/31) in diarrheic patients and 4.9% (4/81) in nondiarrheic (p = 0.04) ones. In diarrheic cases, 27.3% had fever, vomiting and anorexia, whereas 18.2% had fever, anorexia and abdominal pain. One SaV-positive sample was sequenced and classified as GII.1. These results show a high genetic diversity of NoV and higher prevalence of NoV compared to SaV. Our data highlight the importance of NoV and SaV as enteropathogens in São Luís, Maranhão.

Group A rotavirus and norovirus display sharply distinct seasonal profiles in Belém, northern Brazil

Several viruses have been associated with acute gastroenteritis (AGE), and group A rotavirus (RVA) and nor-ovirus (NoV) are the most prevalent. This study aimed to assess their prevalence among children hospitalised for diarrhoea during a three-year surveillance study. From May 2008-April 2011, overall positivity rates of 21.6% (628/2904) and 35.4% (171/483) were observed for RVA and NoV, respectively. The seasonality observed indicated distinct patterns when both viruses were compared. This finding may explain why hospitalisation for AGE remains constant throughout the year. Continuous AGE monitoring is needed to better assess the patterns of infection.

Occurrence of strongyloidiasis among patients with HTLV-1/2 seen at the outpatient clinic of the Núcleo de Medicina Tropical, Belém, State of Pará, Brazil

Introduction This study investigated the occurrence of Strongyloides stercoralis infestation and coinfection with HTLV-1/2 in Belém, Brazil. Methods S. stercoralis was investigated in stool samples obtained from individuals infected with HTLV-1/2 and their uninfected relatives. Results The frequency of S. stercoralis was 9% (9/100), including six patients infected with HTLV-1 (14.3%), two patients infected with HTLV-2 (11.1%), and one uninfected relative. Two cases of hyperinfestation by S. stercoralis were characterized as HTLV-1. Conclusions These results support the need for the routine investigation of S. stercoralis in patients with HTLV-1, in an attempt to prevent the development of severe forms of strongyloidiasis. .

Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

Detection of corona-like virus in a case of flaccid paraparesis in Belém, Pará State, Brazil / Detecção de virus corona-like em um caso de paraparesia flácida em Belém, Estado do Pará, Brasil

In this study, we analyzed a fecal sample of a female infant with paralysis and other clinical symptoms that resembled poliomyelitis. Negative staining electron microscopy showed viral particles with a diameter of approximately 120 nm and displaying a crown-like appearance with surface projections. Ultrathin sections showed particles budding from the membranes of the Golgi apparatus. Based on these results, we propose the association of this virus with the neurological disorder and tentatively assign it to the Coronaviridae family. Further studies are required on this proposed relationship.

Neste estudo, analisamos uma amostra fecal de criança do sexo feminino com paralisia e outros sintomas clínicos que se assemelharam à poliomielite. A microscopia eletrônica (contrastação negativa) mostrou partículas com 120 nm de diâmetro, exibindo projeções na superfície semelhantes a uma coroa. Cortes ultrafinos mostraram partículas brotando do complexo de Golgi. Com base nesses resultados, propomos a associação deste vírus com o distúrbio neurológico e o associamos provisoriamente à família Coronaviridae. Estudos adicionais são necessários para esclarecer a relação proposta.

Reanálise da vacina tetravalente (RRV-TV) no contexto da prevenção das gastrenterites por rotavírus / Review of a tetravalent vaccine (RRT-TV) for prevention of gastroenteritis caused by rotavirus

Os rotavírus são considerados a principal causa de gastrenterite grave em crianças abaixo de cinco anos, principalmente nos países em desenvolvimento. A vacinação nos primeiros meses de vida se constitui na medida mais efetiva em saúde pública para o controle e prevenção das infecções por tais agentes. Não obstante o recente licenciamento de duas vacinas para uso corrente em lactentes (Rotarix® e RotaTeq®), as pesquisas prosseguem com novas alternativas de prevenção e tratamento. Neste contexto, procedeu-se à reanálise da Rhesus-Human Reassortant Rotavirus Tetravalent Vaccine (RRV-TV), com ênfase à eficácia clínica frente aos parâmetros clínicos, aos sorotipos mais prevalentes na região, à ocorrência de eventos adversos graves (intussuscepção) e a proteção seletiva aos quadros de maior gravidade. Os dados clínicos e epidemiológicos foram obtidos das fichas clínicas de 91 episódios diarreicos em crianças no âmbito de uma investigação prévia conduzida em Belém, Pará. Foram considerados como indicadores de gravidade, os parâmetros clínicos e um sistema de escores, comumente aplicado aos estudos de eficácia da RRV-TV. Os resultados mais expressivos do estudo, como a significativa proteção (p 14 relacionados ao sorotipo G2, a eficácia de 75 por cento contra os episódios mais graves, são discutidos à luz do contexto atual dos conhecimentos sobre o tema.

Rotaviruses are considered the leading cause of severe gastroenteritis in children under five years of age, especially in developing countries. Vaccination in the first months is the most effective public health action for the control and prevention of infections by such agents. Despite the recent licensing of two vaccines for use in infants (Rotarix® and Rota Teq®), researchers continue to seek new alternatives for prevention and treatment. Herein, we provide a review of the Rhesus-Human Reassortant Rotavirus Tetravalent Vaccine (RRV-TV), with an emphasis on its clinical efficacy as regards clinical parameters, the most prevalent serotypes in the region, the occurrence of severe adverse events (e.g., intussusception), and selective protection in the most severe cases. The clinical and epidemiological data were obtained from medical records pertaining to 91 episodes of diarrhea among children in a previous investigation conducted in Belém, Pará State, Brazil. Clinical patterns and a scoring system commonly used in studies on the efficacy of RRV-TV were considered as indicators of severity. The most impressive results of this study, such as a significant protection (p 14 related to serotype G2, a 75 percent efficacy rate against severe episodes, and the non-occurrence of intussusception, are discussed in the context of current knowledge on this issue.

Molecular characterization of norovirus, sapovirus and astrovirus in children with acute gastroenteritis from Belém, Pará, Brazil / Caracterização molecular de norovírus, sapovírus e astrovírus em crianças com gastroenterite aguda em Belém, Pará, Brasil

The importance of norovirus (NoVs), sapovirus (SaVs) and human astrovirus (HAstVs) as causes of gastroenteritis outbreaks are already well-defined, but a few studies have described sporadic cases of acute gastroenteritis caused by these viral entities. The aim of this study was to determine the role of these viruses in the etiology of acute gastroenteritis in children enrolled to participate in hospital – and emergency department – based intensive surveillance carried out in Belém, Brazil, from March to September 2003. A total of 305 stool specimens from patients with severe gastroenteritis were collected and screened by reverse transcription followed by polymerase chain reaction (RT-PCR), using the specific primers Mon 269 and Mon 270 for HAstVs, p289 and p290 for human calicivirus (HuCVs), and Mon 431/433 and Mon 432/434 for NoVs. Sequencing of RT-PCR HAstV, HuCVs and NoVs amplicons was carried out using the same primers. Of the 305 samples tested, 96 (31.5 percent) were positive, with 51 diagnosed as HuCVs, 40 as HAstVs and five as mixed infections. Of the 56 (18.4 percent) HuCVs sequenced, 30 were NoVs (9.8 percent) of genogroups GI-4 and GII-4, and 15 (4.9 percent) were SaVs of types GI-1, GI-2 and GII-1. HAstVs, including genotypes 1, 8 and 2, were detected in 45 (14.7 percent) samples. This study has highlighted the importance of these viruses as causes of acute gastroenteritis and established the circulation of different genotypes during the study period. These results reinforce the need for establishing an intensive surveillance for gastroenteritis caused by these viruses to assess the burden of disease and to monitor the circulation of genotypes.

A importância dos norovírus (NoVs), sapovírus (SaVs) e astrovírus humanos (HAstVs) como causa de surtos de gastroenteritis já está bem definida. Entretanto, poucos estudos têm descrito casos esporádicos de gastroenterites aguda causados por esses agentes. O objetivo deste estudo foi determinar o papel destes vírus na etiologia da gastroenterite aguda em crianças atendidas durante uma vigilância intensiva realizada em hospitais e ambulatórios de Belém, Brasil, de março a setembro de 2003. Um total de 305 espécimes fecais de pacientes com gastrenterite grave foram coletados e testados por reação em cadeia da polimerase precedida de transcrição reversa (RT-PCR), utilizando iniciadores específicos Mon 269 e Mon 270 para os HAstVs; p289 e p290 para os calicivírus humanos (HuCVs); e Mon 431/433 e Mon 432/434 para os NoVs. Sequenciamento dos amplicons de HAstV, HuCVs e NoVs, obtidos por RT-PCR, foi realizado usando os mesmos iniciadores. Das 305 amostras testadas, 96 (31,5 por cento) apresentaram resultados positivos, sendo que 51 diagnosticadas como HuCVs, 40 como HAstVs e cinco infecções mistas. Das 56 (18,4 por cento) amostras de HuCVs sequenciadas, 30 foram NoVs (9,8 por cento) pertencentes aos genogrupos GI-4 e GII-4, e 15 (4,9 por cento) SaVs dos grupos GI-1, GI-2 e GII-1. HAstVs foram detectados em 45 (14,7 por cento) das amostras, incluindo os genótipos 1, 8 e 2. Esta pesquisa ressalta a importância destas viroses como causa de gastrenterite aguda e demonstra a circulação de diferentes genótipos durante o período de estudo. Estes resultados reforçam a necessidade de se estabelecer uma vigilância intensiva das gastrenterite causadas por estes vírus, de forma a poder avaliar o impacto da doença e monitorar os genótipos circulantes.

Molecular characterization of G1 human rotaviruses detected in children from Belém, Pará, Brazil / Caracterização molecular de rotavírus humanos do tipo G1 detectados em crianças de Belém, Pará, Brasil

Rotavirus is responsible for 40 percent of gastroenteritis infections worldwide, resulting in 611 thousand deaths annually among infants and young children. The aim of the present study was to perform molecular characterization of strains of the most common circulating rotavirus genotype (G1), which was obtained from children participating in studies previously conducted in Belém, northern Brazil over a 21-year period (1982 to 2003). G1 type rotavirus was detected by polyacrylamide gel electrophoresis, enzyme immunoassay and by reverse transcription polymerase chain reaction for the VP7 and VP4 genes. Of 798 specimens that were found to be positive for rotavirus, 330 (41 percent) had G1-specificity by EIA using monoclonal antibodies. A total of 148 G1 strains were analyzed by reverse transcription polymerase chain reaction. Electropherotypes and P genotypes characterization of G1 rotavirus occurred at frequencies of 78 percent and 88 percent, respectively. Three long electropherotype varieties were identified, with the L1 variety the most frequently found (79 percent). The G1P[8] combination was the most frequent, responsible for 64 percent of cases. Mixed infections of G1P[6]+P[8], G1P[4]+P[8], G1P[4]+P[6] and G1P[4]+P[6]+P[8] were found in 11 (7 percent), 11 (7 percent), 3 (2 percent) and 1 (0.6 percent) samples, respectively. One sample displaying a mixed G1+G4 infection was found. To our knowledge, this is the first study to focus on G1 rotavirus molecular characterization in Brazil. Our findings provide information that will allow a better understanding of the molecular diversity of G1 rotavirus infections in our region.

Os rotavírus são responsáveis por 40 por cento das ocorrências de gastroenterites infantil no mundo, resultando em 611 mil mortes anualmente, e o rotavírus do tipo G1 representa o seu genótipo circulante mais comum. O objetivo do presente artigo foi realizar a caracterização molecular das amostras de rotavírus do tipo G1 obtidas de crianças que participaram de estudos anteriormente conduzidos na Cidade de Belém, norte do Brasil, por um período de 21 anos (1982 a 2003). O rotavírus do tipo G1 foi detectado por meio de eletroforese em gel de poliacrilamida, ensaio imunoenzimático (EIA) e reação em cadeia da polimerase precedida da transcrição reversa para os genes VP7 e VP4. Dos 798 espécimes positivos para rotavírus, 330 (41 por cento) apresentavam especificidade G1 por EIA, usando anticorpos monoclonais. Um total de 148 amostras do tipo G1 foram analisadas por meio da reação em cadeia da polimerase precedida da transcrição reversa. A caracterização dos eletroferotipos e genótipos P dos rotavírus do tipo G1 ocorreu em frequências de 78 por cento e 88 por cento, respectivamente. Três variedades de eletroferotipos longos foram identificados, sendo L1 a predominante (79 por cento). A combinação G1P[8] foi a mais frequente, responsável por 64 por cento dos casos. As infecções mistas G1P[6]+P[8], G1P[4]+P[8], G1P[4]+P[6] e G1P[4]+P[6]+P[8] foram encontradas em 11 (7 por cento ), 11 (7 por cent), 3 (2 percent) e 1 (0,6 por cento) amostras, respectivamente. Uma amostra apresentando infecção mista G1+G4 foi identificada. Ressalte-se que este é o primeiro estudo a abordar a caracterização molecular de rotavírus do tipo G1 no Brasil. Nossos achados permitirão melhor compreensão a respeito da diversidade molecular associada às infecções por rotavírus do tipo G1 em nossa região.

Ocorrência de adenovírus em crianças com gastrenterite aguda grave na cidade de Belém, Pará, Brasil / Detection of adenoviruses in children with severe acute gastroenteritis in the City of Belém, Pará State

As gastrenterites são uma das principais causas de doença infantil em todo mundo. Estudos epidemiológicos detectaram adenovírus em 2 por cento a 22 por cento dos casos de diarreia aguda infantil em hospitais e ambulatórios clínicos. Eles são responsáveis por 50 por cento dos casos de intussuscepção intestinal pediátrica. O objetivo do estudo foi detectar a presença desses vírus nas amostras fecais de 380 crianças menores de 3 anos de idade, com quadro de gastrenterite, em Belém, com ênfase no sorotipo 40/41. As amostras foram provenientes de um estudo de vigilância hospitalar e ambulatorial realizado pelo Instituto Evandro Chagas no período de março a setembro de 2003. Foram usadas as técnicas de EIA e imunocromatografia para triagem; e cultura de células e PCR para tipagem. Os adenovírus foram encontrados em 6,3 por cento (24/380) das amostras. Já o adenovírus entérico (AdE) estava presente em 3,7 por cento (14/380) das amostras testadas, equivalendo a 58,3 por cento (14/24) dos casos positivos, o que demonstrou que esse vírus é causa de grande parte dos casos de gastrenterites em crianças. A técnica mais sensível foi a PCR, sendo capaz de definir sorotipos de cinco amostras que estavam sem definição. Os AdEs predominaram na faixa etária de 18-24 meses e o maior número de casos ocorreu no mês de março de 2003, com tempo de hospitalização de maior frequência em torno de seis dias. Os resultados obtidos neste estudo confirmam a circulação desse vírus na cidade de Belém, Pará, demonstrando a importância deles como causa de gastrenterite em crianças.

Gastroenteritis is one of the major childhood diseases worldwide. Epidemiological studies have detected adenoviruses in 2 per cent to 22 per cent of cases of acute infantile diarrhea in hospitals and outpatient clinics. Adenoviruses are responsible for 50 per cent of cases of pediatric intestinal intussusception. The aim of this study was to detect the presence of these viruses in stool samples from 380 children younger than three years old with symptoms of gastroenteritis in Belém, with an emphasis on serotype 40/41. The samples came from a surveillance study conducted by the hospital and outpatient clinic of the Instituto Evandro Chagas from March to September 2003. We used EIA and an immunochromatographic technique for screening, and cell culture and PCR for typing. Adenoviruses were found in 6.3 per cent (24/380) of the samples. Enteric adenoviruses (EAds) were present in 3.7 per cent (14/380) of tested samples, which corresponded to 58.3 per cent (14/24) of positive cases. This demonstrated that this virus is the cause of the majority cases of gastroenteritis in children. The most sensitive technique was PCR, which was able to define the serotypes of five samples that were not defined by other methods. EAds predominated in the age group of 18-24 months, and the highest number of cases occurred in March 2003. The average time of hospitalization was approximately six days. The results of this study confirm the circulation of the virus in Belém, Pará State, demonstrating theimportance of adenoviruses as a cause of gastroenteritis in children

Economic impact of a rotavirus vaccine in Brazil.

The study was done to evaluate the cost-effectiveness of a national rotavirus vaccination programme in Brazilian children from the healthcare system perspective. A hypothetical annual birth-cohort was followed for a five-year period. Published and national administrative data were incorporated into a model to quantify the consequences of vaccination versus no vaccination. Main outcome measures included the reduction in disease burden, lives saved, and disability-adjusted life-years (DALYs) averted. A rotavirus vaccination programme in Brazil would prevent an estimated 1,804 deaths associated with gastroenteritis due to rotavirus, 91,127 hospitalizations, and 550,198 outpatient visits. Vaccination is likely to reduce 76% of the overall healthcare burden of rotavirus-associated gastroenteritis in Brazil. At a vaccine price of US$ 7-8 per dose, the cost-effectiveness ratio would be US$ 643 per DALY averted. Rotavirus vaccination can reduce the burden of gastroenteritis due to rotavirus at a reasonable cost-effectiveness ratio.

Group A rotavirus genotypes and the ongoing Brazilian experience: a review

Brazil was the first Latin American country to introduce universal group A rotavirus (RV-A) vaccination in March 2006, resulting in a unique epidemiological scenario. Since RV-A first identification in Brazil, 2,691 RV-A-positive stool samples, collected between 1982- 2007, were typed by independent research groups throughout the country. In the pre-vaccination era, 2,492 RV-A-positive samples collected from 1982-2005 were successfully typed, while 199 samples were analyzed from 2006-2007. According to the reviewed studies, there were two important times in the pre-vaccination era: (i) the period from 1982-1995, during which the detection of G5P[8] RV-A, in addition to the classical genotypes G1-4, challenged vaccine development programs; and (ii) the period from 1996-2005, during which genotype G9P[8] emerged, following a global trend. The rate of G2P[4] RV-A detection decreased from 26 percent (173/653) during 1982-1995 to 2 percent (43/1,839) during 1996-2005. The overall detection rate of RV-A genotypes from 1982-2005 was as follows: 43 percent (n = 1,079) G1P[8]/G1P[not typed (NT)]; 20 percent (n = 488) G9P[8]/G9P[NT]; 9 percent (n = 216) G2P[4]/G2P[NT]; 6 percent (n = 151) G3P[8]/G3P[NT]; 4 percent (n = 103) G4P[8]/G4P[NT]; and 4 percent (n = 94) G5P[8]/G5P[NT]. Mixed infections accounted for 189 (7 percent) of the positive samples, while atypical G/P combinations or other genotypes, including G6, G8, G10 and G12, were identified in 172 (7 percent) samples. The initial surveillance studies carried out in several Brazilian states with RV-A-positive samples collected in 2006 and 2007 show a predominance of G2P[4] strains (148/199 or 74 percent). Herein, we review RV-A typing studies carried out since the 1980s in Brazil, highlighting the dynamics of RV-A strain circulation profiles before and early after universal use of RV-A vaccine in Brazil.

First detection of a human astrovirus type 8 in a child with diarrhea in Belém, Brazil: comparison with other strains worldwide and identification of possible three lineages

This study describes the genetic relationships of the first human astrovirus type-8 (HAstV-8) detected in Belém-Brazil, during a public hospital-based study. This strain was compared with other HAstV-8 strains identified elsewhere which have sequences available at GeneBank. The regions ORF1a (primers Mon348/Mon340) and ORF2 (primers Mon269/Mon270) were analyzed by nucleotide sequencing and a high similarity rate was observed among the Belém strain and other HAstV-8 strains. In ORF1a, homology values of 93-100 por cento were detected, and in ORF2 96-99 por cento. Considering the sequence variation (7 por cento) observed in ORF2 region, it was suggested that HAstV-8 strains could be divided in three different lineages.

Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana / Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

OBJETIVO: Determinar a segurança, imunogenicidade e eficácia de duas doses da vacina contra o rotavírus em lactentes brasileiros saudáveis. MÉTODOS: Foi realizado um estudo randomizado, multicêntrico, duplo-cego e controlado por placebo no Brasil, México e Venezuela. Os lactentes receberam duas doses orais de vacina ou placebo aos 2 e 4 meses de idade, juntamente com as imunizações de rotina, exceto a vacina oral contra poliomielite (VOP). O presente estudo relata apenas os resultados obtidos em Belém, Brasil, onde o número de indivíduos por grupo e os títulos da vacina viral foram os seguintes: 194 (104,7 unidades formadoras de focos - UFF), 196 (10(5,2) UFF), 194 (10(5,8) UFF) e 194 (placebo). A resposta de anticorpos anti-rotavírus (anti-RV) foi avaliada em 307 indivíduos. A gravidade clínica dos episódios de gastroenterite (GE) foi determinada através de um escore com 20 pontos, onde um valor > 11 foi considerado como GE grave. RESULTADOS: As taxas de sintomas gerais solicitados foram semelhantes tanto nos indivíduos que receberam a vacina como naqueles a quem se administrou placebo. Aos 2 meses após a segunda dose, ocorreu resposta em termos de IgA sérica para RV em 54,7 a 74,4 por cento dos vacinados. Não houve interferência na imunogenicidade das vacinas de rotina. A eficácia da vacina contra qualquer gastroenterite por rotavírus (GERV) foi de 63,5 por cento (IC95 por cento 20,8-84,4) para a maior concentração (10(5,8) UFF). A eficácia foi de 81,5 por cento (IC95 por cento 44,5-95,4) contra GERV grave. Em sua maior concentração (10(5,8) UFF), a RIX4414 conferiu uma proteção de 79,8 por cento (IC95 por cento 26,4-96,3) contra GERV grave causada pela amostra G9. CONCLUSÕES: A RIX4414 foi altamente imunogênica com baixa reatogenicidade, e não interferiu na resposta sérica à difteria, tétano, coqueluche, hepatite B e antígenos Hib. Duas doses da RIX4414 conferiram proteção significativa contra a GE grave causada pelo RV.

OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4 percent of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5 percent (95 percentCI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5 percent (95 percentCI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8 percent (95 percentCI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

Vacinas contra rotavírus e papilomavírus humano (HPV) / Vaccines against rotavirus and human papillomavirus (HPV)

OBJETIVOS: Sintetizar as estratégias para a obtenção de uma vacina contra rotavírus e papilomavírus humano (HPV), enfatizando-se o estágio atual das investigações quanto à segurança, reatogenicidade, imunogenicidade e eficácia. FONTE DOS DADOS: Os artigos publicados de 1996 a 2006, particularmente ao longo dos últimos 5 anos, representaram a fonte primária (base de dados: MEDLINE, PubMed, NIH, EUA), conferindo-se destaque aos recentes estudos envolvendo uma vacina contendo rotavírus atenuado de origem humana e dois tipos de vacinas para HPV testadas em humanos: as profiláticas e as terapêuticas. SíNTESE DOS DADOS: Em relação às vacinas contra rotavírus, o contexto de estratégias compreendeu desde as preparações jennerianas até o advento da vacina com rotavírus atenuado de origem humana. Duas vacinas despontam como eficazes e seguras: uma, pentavalente, envolvendo vírus de bovinos e do homem; outra, de rotavírus atenuado oriundo da espécie humana, sendo que esta é avaliada em mais de 70.000 crianças no mundo. As vacinas contra HPV profiláticas visam impedir a infecção por esses vírus, enquanto que as vacinas terapêuticas pretendem tratar o indivíduo já infectado ou até o portador de uma lesão causada por HPV. As pesquisas com vacinas profiláticas começaram há alguns anos nos EUA e, hoje, aproximadamente 25.000 mulheres, em vários países, participam de estudos sobre essa vacina, que até o momento tem se mostrado segura, bem tolerada, altamente imunogênica e eficaz contra os tipos de HPV que causam as verrugas genitais e 70 por cento dos casos de câncer do colo do útero. CONCLUSÕES:Uma vacina eficaz e segura contra rotavírus resultará em impacto significativo quanto à doença grave por esse enteropatógeno. Um programa global de imunizações que consiga atingir 60 a 80 por cento das crianças durante os próximos 10 anos pode reduzir em pelo menos 50 por cento as hospitalizações e a mortalidade por rotavírus. Antecipa-se que a implementação de vacinas de elevada eficácia na prevenção de tumores benignos e malignos causados por alguns tipos de HPV leve a uma queda acentuada das taxas desses tumores, os quais afetam milhões de pessoas em todo o mundo.

Prevalence and genetic diversity of astroviruses in children with and without diarrhea in São Luís, Maranhão, Brazil

Human astroviruses (HAstV) have been increasingly identified as important etiological agents of acute gastroenteritis in children up to five years old. The aim of this study was to determine the prevalence and genotype diversity of HAstV in children with symptomatic and asymptomatic infections in São Luís, Maranhão, Brazil. From June 1997 to July 1999 a total of 183 fecal samples 84 from symptomatic and 99 from asymptomatic children were tested by enzyme immunoassay for HAstV. Prevalence rates were found to be 11 and 3 percent for symptomatic and asymptomatic children, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out in 46 specimens (26 symptomatic and 20 asymptomatic) including the 12 samples that were positive by enzyme immunoassay (EIA). The overall positivity yielded by both methods was 8 percent (15/184); of these, 11 percent (9/84) for symptomatic and 5 percent (5/99) for those without symptoms or signs. Sequence analysis of amplicons revealed that HAstV-1 genotype was the most prevalent, accounting for 60 percent of isolates. Genotypes 2, 3, 4, and 5 were also detected, as one single isolate (10 percent) for each type. Variations in the sequences were observed when Brazilian isolates were compared to prototype strains identified in the United Kingdom. No seasonal pattern of occurrence was observed during these two years of study, and peak detection rate was observed in children aged between 3 and 6 months in the symptomatic group, and between 18 and 24 months in the controls.