G1P[8] Rotavirus in children with severe diarrhea in the post-vaccine introduction era in Brazil: Evidence of reassortments and structural modifications of the antigenic VP7 and VP4 regions.

Worldwide rotaviruses A (RVA) are responsible for approximately 215,000 deaths annually among children aged <5 years. RVA G1P[8] remains associated with >50% of gastroenteritis cases in this age group. The aim of this study was to assess the genetic variability of G1P[8] strains detected in children with severe diarrhea in Belém, Pará, Brazil, during the post-rotavirus vaccine introduction era. Phylogenetic analysis clustered the VP4 and VP7 genes of 40 samples selected between 2009 and 2011 into lineages found to be different from the Rotarix® vaccine strain. A detailed investigation of their complete genotype constellations identified 2 reassortant viruses (5%), resulting from reassortments between the genogroups Wa-like and DS-1-like (G1-P[8]-I1-R2-C1-M1-A1-N1-T2-E1-H1) and Wa-like and AU-1-like (G1-P[8]-I1-R3-C1-M1-A1-N1-T1-E1-H1) genotype constellations. A comparison of the amino acid residues presents in the antigenic epitopes of VP7 and VP4, showed differences in the electrostatic charges distribution, between wild type Brazilian strains and the Rotarix® and RotaTeq® vaccine strains. These findings reflect the structural analyses of the antigenic regions of VP7 and VP4 of the RVA G1P[8] in children with gastroenteritis in Northern Brazil raising the hypothesis that structural modifications at these sites over time may account for the emergence of new strains that could possibly pose a challenge to current vaccines.

Outbreak of acute gastroenteritis in young children with death due to rotavirus genotype G9 in Rio Branco, Brazilian Amazon region, 2005.

BACKGROUND: An epidemic of acute gastroenteritis occurred in Rio Branco City, Acre State, in Brazil's Amazon region in 2005. An investigation was conducted to confirm the etiology and identify possible risk factors for death. METHODS: Rio Branco municipality surveillance data for the period May to October 2005 were reviewed. In a case-control study, children who died following acute gastroenteritis were compared to age-matched controls with acute gastroenteritis who survived. Rotavirus A (RV-A) was investigated in 799 stool samples and genotyped by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The cumulative incidence of diarrhea in children aged <5 years was 21%. A fatal outcome was significantly associated with uncovered household water storage containers. RV-A was identified in 88% of samples and G9 was the prevalent genotype (71%). CONCLUSIONS: Oral rehydration solution and boiling or chlorinating drinking water likely limited mortality. This epidemic was caused by RV-A genotype G9. After the outbreak, a rotavirus vaccine was introduced into the official childhood immunization schedule in Brazil.

Rotavirus serotype G9 is associated with more-severe disease in Latin America.

The association between rotavirus serotypes and severity is not well established. Analysis of a clinical trial conducted in Latin America points at more-severe disease associated with serotype G9. Thus, demonstration of efficacy against G9 will be an important asset of any rotavirus vaccine to be introduced into a Latin American country or any country where G9 has been shown to be prevalent.

A short report on highlights of world-wide development of RIX4414: a Latin American experience.

An oral, human-derived monovalent (G1P1A) rotavirus vaccine, strain RIX4414, has been developed by GlaxoSmithKline, Rixensart, Belgium. The safety, immunogenicity and efficacy of this vaccine were evaluated in a randomized, double-blind, placebo-controlled, phase IIb trial conducted in Brazil, Mexico and Venezuela. Healthy infants were given two doses of vaccine (104.7, 105.2 or 105.8 ffu) or placebo at age 2 and 4 months, with routine DTPw-HBV and Hib vaccines. OPV was given separately, at least 2 weeks before or after administration of the study vaccine. A total of 2155 infants were enrolled, of whom 1618 received one of the three vaccine viral concentrations and 537 were given placebo. Analysis of efficacy included diarrheal episodes occurring from 2 weeks after second dose until one year of age. Efficacy rates against any rotavirus gastroenteritis, severe rotavirus gastroenteritis and hospitalizations for rotavirus disease were as high as 70% (46-84%; 95%CI), 86% (63-96%; 95%CI), and 93% (54-100%; 95%CI), respectively. For non-G1 (mainly G9) serotypes, RIX4414 vaccine conferred protection as high as 83% (40-97%; 95%CI) against severe gastroenteritis. A decrease was noted in the incidence of severe rotavirus-related gastroenteritis after first dose. It is demonstrated that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis and hospitalization, including disease caused by non-G1 strains, namely G9 serotypes.

Tetravalent rhesus-human rotavirus vaccine (RRV-TV) in Belém, Brazil: efficacy against prevailing P and G genotypes.

To determine the efficacy of a reassortant rhesus-human tetravalent rotavirus vaccine (RRV-TV) (4 x 10(4) pfu/dose) against P and G rotavirus genotypes, 90 positive samples were tested using reverse transcription-polymerase chain reaction. The efficacy of the RRV-TV vaccine against P[8] and G1 individually or in binary combination P[8], G1 was 72 per cent (p < 0.005) 61 per cent (p < 0.013), and 70 per cent (p < 0.009), respectively, only for the first year of follow-up. In the second year, as well as after 2 years of follow-up, no efficacy was observed to these genotypes. These data indicate that further studies with rotavirus vaccines should focus on the molecular characterization of rotaviruses genotypes, in order to see whether or not cross-protection among different G and P genotypes may occur as a result of common bearing of VP4 specificities.

Detection and characterization of rotavirus G and P types from children participating in a rotavirus vaccine trial in Belém, Brazil.

This study sought the characterization of rotaviruses in a trial with a tetravalent rhesus-human rotavirus vaccine in Belém, Brazil in children who received three doses of vaccine or placebo in the 1st, 3rd and 5th months of life. Rotavirus electropherotypes, subgroups, G serotypes, G, [P] and [P], G genotypes were determined in 93.3%, 95.9%, 93.3%, 73.3%, 95.5% and 92.2% of isolates, respectively. Serotypes G1, G2 and G4 were detected in 58.9%, 30% and 4.4% of the cases, respectively. Rotavirus genotype G5 was detected for the first time in Northern region in 4.4% of the infections. Rotavirus genotypes P[8], P[4], P[6] and P[8 + 6] were detected in 54.5%, 26.7%, 12.2%, and 2.2% of the cases, respectively. The predominant genotypes were P[8], G1 and P[4], G2 with 53% and 26.6% of the infections, respectively. Unusual strains accounted for 20.5% including P[4], G1, P[6], G1, P[6], G4, P[6], G5, P[8], G2, P[8], G5. Mixed infections involving P[8 + 6], G2 and P[8 + 6], G1 were also noted. The neonatal P[6] strains associated with diarrhea were detected among children aged 9-24 months. To our knowledge, this study represents the first in Brazil to analyse, on molecular basis, rotavirus genotypes from children participating in a rotavirus vaccine trial. These results are of potential importance regarding future rotavirus vaccination strategies in Brazil.

Detection and characterization of Rotavirus G and P types from children participating in a Rotavirus vaccine trial in Belém, Brazil

This study sought the characterization of rotaviruses in a trial with a tetravalent rhesus-human rotavirus vaccine in Belém, Brazil in children who received three doses of vaccine or placebo in the 1st, 3rd and 5th months of life. Rotavirus electropherotypes, subgroups, G serotypes, G, [P] and [P],G genotypes were determined in 93.3 percent, 95.9 percent, 93.3 percent, 73.3 percent, 95.5 percent and 92.2 percent of isolates, respectively. Serotypes G1, G2 and G4 were detected in 58.9 percent, 30 percent and 4.4 percent of the cases, respectively. Rotavirus genotype G5 was detected for the first time in Northern region in 4.4 percent of the infections. Rotavirus genotypes P[8], P[4], P[6] and P[8+6] were detected in 54.5 percent, 26.7 percent, 12.2 percent, and 2.2 percent of the cases, respectively. The predominant genotypes were P[8],G1 and P[4],G2 with 53 percent and 26.6 percent of the infections, respectively. Unusual strains accounted for 20.5 percent including P[4],G1, P[6],G1, P[6],G4, P[6],G5, P[8],G2, P[8],G5. Mixed infections involving P[8+6],G2 and P[8+6],G1 were also noted. The neonatal P[6] strains associated with diarrhea were detected among children aged 9-24 months. To our knowledge, this study represents the first in Brazil to analyse, on molecular basis, rotavirus genotypes from children participating in a rotavirus vaccine trial. These results are of potential importance regarding future rotavirus vaccination strategies in Brazil

Detection of enteroviruses in cases of neurological disorders in the State of Pará, Brazil.

Eighty-one cerebrospinal fluid (CSF) samples mainly from cases of aseptic meningitis and motor deficiency syndrome were sent to the Virology Section of Evandro Chagas Institute, Belém Pará, in the period of January 1995 to January 1996 in order to isolate viruses. All samples were inoculated onto HEp-2 cell culture and newborn mice, with negative results. The probability of isolating viruses by these methods is reduced because of the low concentration of viral particles in these specimens. In order to obtain more information about the etiology of these cases, a group of 23 samples were selected to be tested by a more sensitive technique than the virus isolation - the reverse transcription polymerase chain reaction (RT-PCR). Specific primers directed to conserved regions in the enterovirus genome were used, considering that this group of viruses is frequently associated with these neurological disorder. The age of the patients ranged from 1 to 55 years and nearly all of them lived in Belém, State of Pará, North of Brazil. Of 15 samples analyzed by RT PCR nine (60%) were positive; of these, 6 (66.6%) had motor deficiency and 3 (33.3%) developed aseptic meningitis. These results show that it is important to investigate enterovirus as cause of these syndromes.

[Rotavirus infection in Brazil: epidemiology and challenges for its control]. / Epidemiologia das infecções por rotavírus no Brasil e os desafios para o seu controle.

Worldwide, rotaviruses account for 600,000 to 870,000 deaths per year among infants and young children. In Brazil, rotaviruses were first seen in 1976 by scanning electron microscopy of stool samples from diarrheic infants in Belém, Pará. Hospital-based studies have shown that rotaviruses are associated with 12-42% of cases of acute diarrhea. In addition, community-based studies yielded an average of 0.25 rotavirus-related diarrheal episodes per child per year. G types 1 to 4 account for about two-thirds of circulating strains, but the (unusual) P[8],G5 genotype has been claimed to cause over 10% of rotavirus diarrheal episodes. It has been shown that over 70% of children develop rotavirus antibodies by the age of 4-5 years. The tetravalent rhesus-human rotavirus vaccine (RRV-TV) conferred 35% protection according to a two-year follow-up study in Belém, Pará, Brazil, but reached an efficacy of 60% during the first year of life. RRV-TV was also shown to be 75% protective against very severe gastroenteritis in northern Brazil. Vaccination with RRV-TV has been suspended recently in the United States because of the detection of intussusception as a side effect. Therefore, further vaccine trials in Brazil will probably involve rotavirus candidate vaccines other than RRV-TV.

Human herpesvirus 8 in Brazilian Amerindians: a hyperendemic population with a new subtype.

Human herpesvirus 8 (HHV-8) epidemiology in Brazilian Amerindians was studied. Use of an immunofluorescence (IFA) test for latent antibody demonstrated that the prevalence of HHV-8 in 781 Amerindians of diverse tribes (overall, 53% prevalence) was not related to language group or sex but rather increased gradually from 41% in children <10 years of age to 65% in adults >/=30 years of age. In IFA-positive subjects, HHV-8 DNA was detected in 3 (16%) of 19 mononuclear cell samples from peripheral blood and in 1 of 16 saliva samples. The sequences of conserved ORF22 and K6 genes were typical of HHV-8, but the variable K1 gene sequences were only 70%-75% identical to other known HHV-8 strains. Thus, a new HHV-8 subtype, E, is hyperendemic in Brazilian Amerindians, although Kaposi's sarcoma has not been reported. Transmission is probably oral rather than sexual. The limited genetic pool in isolated groups may permit more frequent transmission of a virus with a low prevalence in heterogeneous populations.

Rotavirus vaccines and vaccination in Latin America.

Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV), was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 x 10(4) plaque-forming units (PFU) preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be overcome by giving three doses of the rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary rotavirus vaccine failure in developing countries. Studies in Peru with RRV-TV have shown a trend towards higher vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes. Economic analyses made in the United States indicate that a vaccine that costs less than US$ 9 per dose would lead to a net savings in medical costs. To date, however, cost-benefit studies have not been done in developing countries. In the future, it is possible that some Latin American countries might adapt their polio production facilities to the preparation of rotavirus vaccines for human use. A year after RRV-TV was licensed for vaccination of infants in the United States, the occurrence of intussusception as an adverse event led to the vaccine's withdrawal from the market. The implications of that action, particularly for Latin America, will be addressed in this article, including the need to explore alternative rotavirus candidate vaccines, particularly through the conduct of parallel clinical trials in both developed and developing countries.

Outbreaks of human-herpes virus 6 (HHV-6) infection in day-care centers in Belém, Pará, Brazil.

A total of 730 children aged less than 7 years, attending 8 day-care centers (DCCs) in Belém, Brazil were followed-up from January to December 1997 to investigate the occurrence of human-herpes virus 6 (HHV-6) infection in these institutional settings. Between October and December 1997 there have been outbreaks of a febrile- and -exanthematous disease, affecting at least 15-20% of children in each of the DCCs. Both serum- and- plasma samples were obtained from 401 (55%) of the 730 participating children for the detection of HHV-6 antibodies by enzyme-linked immunosorbent assay (ELISA), and viral DNA amplification through the nested-PCR. Recent HHV-6 infection was diagnosed in 63.8% (256/401) of them, as defined by the presence of both IgM and IgG-specific antibodies (IgM+/IgG+); of these, 114 (44.5%) were symptomatic and 142 (55.5%) had no symptoms (p = 0.03). A subgroup of 123 (30.7%) children were found to be IgM-/IgG+, whereas the remaining 22 (5.5%) children had neither IgM nor IgG HHV-6- antibodies (IgM-/IgG-). Of the 118 children reacting strongly IgM-positive (> or = 30 PANBIO units), 26 (22.0%) were found to harbour the HHV-6 DNA, as demonstrated by nested-PCR. Taken the ELISA-IgM- and- nested PCR-positive results together, HHV-6 infection was shown to have occurred in 5 of the 8 DCCs under follow-up. Serological evidence of recent infections by Epstein-Barr virus (EBV) and parvovirus B19 were identified in 2.0% (8/401) and 1. 5% (6/401) of the children, respectively. Our data provide strong evidence that HHV-6 is a common cause of outbreaks of febrile/exanthematous diseases among children attending DCCs in the Belém area.

Gastroenterite canina - agentes virais nas fezes de cäes diarréicos e näo diarréicos / Canine gastroenteritis - viral agents in feces from diarrheic and non-diarrheic dogs

Foram analisadas 33 amostras de fezes de cäes com diarréia (n=25) e sem diarréia (n=8), de variadas idades e raças, de ambos os sexos, a fim de se determinar a ocorrência de agentes virais considerados causadores da gastroenterite no cäo, suas possíveis associaçöes e a participaçäo no complexo gastroenterite canina, buscando relacionar a etiologia viral com o histórico de vacinaçäo, além do exame clínico dos animais. Utilizou-se microscopia eletrônica nas 33 amostras fecais e o teste ELISA em 71 amostras para detecçäo de antígeno de rotavírus e adenovírus. Partículas virais foram detectadas em 75,8 por cento (25/33) do total de amostras diarréicas ou näo, examinadas à microscopia eletrônica. Em 44 por cento dos espécimes positivos para vírus (11/25), o vírus-like tipo 1 foi o mais detectado nas amostras fecais, seguido por parvovírus (24 por cento). A ocorrência de diarréia com sangue esteve associada a 90,9 por cento dos agentes detectados, variando em freqüência de 25 por cento a 100 por cento dos casos

Reappraisal of the Peruvian and Brazilian lower titer tetravalent rhesus-human reassortant rotavirus vaccine efficacy trials: analysis by severity of diarrhea.

OBJECTIVES AND METHODS: With the purpose of better understanding the efficacy of the lower titer [4 x 10(4) plaque-forming units (pfu)] tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) against diarrheal episodes of different severities, the Peruvian and Brazilian efficacy data were reanalyzed with a 20-point scoring system. Mild, moderate/severe and very severe rotavirus diarrhea were scored as 0 to 8, 9 to 14 and >14, respectively. RESULTS: In the Peruvian study one dose of vaccine yielded 64% (P = 0.04) protection against pure cases of rotavirus disease (i.e. those in which no other enteropathogen was found) with clinical scores ranging from 9 to 14. Protective efficacy against very severe rotavirus gastroenteritis could not be assessed because of the small number of cases. In Brazil there was a trend in preventing "all" and "pure" cases of rotavirus diarrhea scored 9 to 14 (44%, P = 0.06, and 45%, P = 0.08, respectively) and the vaccine was 75% (P = 0.02) protective against pure rotavirus diarrhea scored >14. No protection was observed for mild rotavirus diarrhea (scores <9). These data were compared with those from trials in Venezuela (4 x 10(5) pfu/dose), US (4 x 10(4) pfu/dose and 4 x 10(5) pfu/dose) and Finland (4 x 10(5) pfu/dose). Combining the Peruvian (one dose, pure cases) and Brazilian studies together, the levels of protection against 9- to 14-scored rotavirus diarrhea are comparable with those from the Venezuelan (47%) and American (57, 57 and 65%) efficacy trials. In Brazil the level of protection (75%) against pure, >14-scored rotavirus diarrhea is similar to the efficacy rates yielded in the three US trials (82, 80 and 69%) and the Finnish trial (100%) for episodes of the same severity. CONCLUSIONS: Our reanalysis provides evidence that, at least against moderate/severe rotavirus gastroenteritis, RRV-TV, 4 x 10(4) pfu/dose is potentially as efficacious as RRV-TV, 4 x 10(5) pfu/dose, even in settings with very high rotavirus disease burden. The reanalysis of the Peruvian data suggests that one and three vaccine doses may yield similar efficacy rates. It is also suggested that vaccine efficacy against most severe episodes in Peru and Brazil was not evident because of the trial design used in those studies (i.e. prospective, active home surveillance rather than a catchment trial), resulting in too few cases of severe disease even in the placebo group. To confirm these findings, future trials with this vaccine are necessary in developing countries with high diarrhea morbidity rates. These trials should use catchment designs and focus on the evaluation of the efficacy of one or three doses of RRV-TV against moderate to severe/very severe rotavirus diarrhea.

Hepatitis B virus surface antigen (HBsAg) and antibody (anti-HBs) forming immune complexes in fulminant hepatitis.

This paper reports an unusual pattern of serological HBV markers and the presence of HBsAg/anti-HBs immune complexes in serum samples from two patients with fulminant hepatitis from the Brazilian Western Amazon Basin. The diagnosis was made by both serologic tests and demonstration of antigen/antibody complexes by transmission electron microscopy. Concurrent Delta virus superinfection is also discussed.

Rotavirus subgroups, G serotypes, and electrophoretypes in cases of nosocomial infantile diarrhoea in Belém, Brazil.

From November 1992 to November 1994 stool samples were obtained from 237 children admitted to a public hospital in Belém. Rotaviruses were detected in 19.3 per cent (60/310) of faecal samples. Of these, 32.1 per cent (18/56), 20.9 per cent (38/181), and 5.4 per cent (4/73) were recorded in cases of nosocomial diarrhoea, community-acquired diarrhoea, and controls, respectively. Fifty-two (86.7 per cent) of the 60 rotavirus-positive specimens were subgrouped and the G serotypes of 55 (91.7 per cent) of them were determined. Subgroups I and II were detected in 50 per cent each of the 52 subgrouped strains. G type 2 was present in 46 (83.6 per cent) of the 55 serotyped samples; serotypes G1 and (mixed) G1 and G4 were found in 14.5 per cent and 1.8 per cent, respectively, of these specimens. Viral RNA electrophoresis showed 14 distinct patterns, including 56.7 per cent (34/60) and 43.3 per cent (26/60) of long and short profiles, respectively. In 40 (66.6 per cent) of the 60 rotavirus-positive faecal samples no enteropathogens other than rotavirus were detected. There was an increased incidence of rotavirus infection from July 1993 to February 1994. The rotavirus-related episodes of diarrhoea were more severe than those of other aetiology and greater clinical severity was not related to a specific G type, subgroup, or electrophoretype.

Survey of Parvovirus B19 Infection in a Cohort of Pregnant Women in Belém, Brazil.

In our study, 300 pregnant women were screened for the presence of human parvovirus B19 IgG and IgM antibodies by an enzyme-linked immunosorbent assay (ELISA). Overall, 253 (84.3%) were found to be IgG-positive and IgM-negative (IgG+gM ), 42 (14%) had neither IgG nor IgM antibodies (IgG /IgM ) and 5 (1.7%) were both IgM- and IgG-positive (IgG+/IgM+). Maternal serology was performed routinely for cytomegalovirus, rubella, toxoplasmosis and syphilis. All IgG /IgM and IgG+/IgM+ women were followed up till the time of delivery, venous blood sample being taken monthly from each one; one IgG /IgM mother seroconverted to IgG+/IgM and B19 DNA was detected by nested polymerase chain reaction technique (PCR) in her serum. All babies born to IgG+/IgM+ mothers (and from that who seroconverted) were IgG+IgM , no B19 DNA could be detected in their sera and no adverse effects were documented either by ultrasonographic examination or the detection of maternal serum alpha-fetoprotein. While 5 of these mothers delivered normal children at term, one gave birth to a premature (low-weight) baby who developed severe anemia and had convulsions; this mother was found to have toxoplasma-specific IgM. As based on serial testing of sera, it is notable that B19 IgM may last up to six months. Our data indicates a low incidence rate of B19 infection in pregnancy in our region, at least during interepidemic periods. In addition, it suggests that recent B19 infection represents a low risk for the development of adverse fetal outcomes.

An outbreak of group C rotavirus gastroenteritis among children attending a day-care centre in Belém, Brazil.

In August 1993, an outbreak of group C rotavirus-associated gastroenteritis occurred among children attending a day-care centre in Belém, Brazil. Of the 64 children, 21 (33%) became ill. Group C rotavirus was identified in faecal specimens from 8 (38%) children with diarrhoea by electron microscopy (EM) and an enzyme immunoassay (EIA), using antibodies specific to the Cowden strain of porcine group C rotavirus. By polyacrylamide gel electrophoresis (PAGE), a pattern similar to that of group C rotavirus was observed in 5 (62.5%) of the 8 EM- and EIA-positive samples. These 5 faecal samples were confirmed to be positive for group C rotavirus by reverse transcriptase-polymerase chain reaction, using specific VP6 and VP7 primers. This is the first report of an outbreak of diarrhoea in North Brazil associated with group C rotavirus. These findings suggest that group C rotavirus may be an important aetiological agent of diarrhoea in this region, which requires further study.

[Rotavirus: clinical features and prevention] / Rotavírus: aspectos clínicos e prevenção.

OBJECTIVES: This report was prepared with the main objective of making an extensive review of both clinical features and prevention of rotavirus gastroenteritis. In addition, it provides an evaluation about the potential for introduction of the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) in the developing countries. METHODS: The main source of information was the most relevant articles published in both national and international journals, as well as selected official reports from the World Health Organization. With regard to rotavirus vaccines, particular emphasis has been placed on the results available from studies carried out during the past five years. Notice we have stressed the epidemiological features of rotavirus infections in Brazil. RESULTS: As a background for the main subjects of this report - clinical features and prevention - available general information on rotavirus infections are briefly discussed in the Introduction. This includes an overview of the etiological agent, epidemiology, immunity and laboratory diagnosis. A detailed description of the typical symptomatic syndrome is made, as well as of other (unusual) clinical manifestations of rotavirus illness. We also discuss the rotavirus candidate vaccines that have been evaluated to date, highlighting the most significant observations which resulted from field trials with the RRV-TV in several countries. The potential for large-scale use of RRV-TV in developing countries is also discussed, focusing mainly on the epidemiological characteristics of rotavirus disease in these regions. CONCLUSION: Rotaviruses are the leading cause of severe gastroenteritis in infants and young children in both industrialized and lessdeveloped countries; in the latter regions, rotavirus diarrhoeal disease represents a major cause of mortality. There is currently a consensus that attempts at prevention need to be directed toward the development of an effective rotavirus vaccine, for large-scale use, that would primarily protect children (aged 0 to 2 years) against severe rotavirus gastroenteritis. In this regard, results from a recent reevaluation of the Peruvian and Brazilian lower-titer RRV-TV efficacy data are promising. Although the RRV-TV ("Rotashield(R)") (recently licensed for general use in U.S.A.) seems to be currently the most promising rotavirus vaccine, it has been suggested that further trials with this vaccine should be conducted in Africa and Asia (efficacy studies) and Latin America [immunogenicity and effectiveness (efficacy under real conditions in a given setting)]. In addition, it is of paramount importance to establish in these regions a surveillance system to monitor the circulating rotavirus strains.

Detection of enteroviral sequence in endomyocardial tissues from patients with cardiac diseases in northern Brazil.

In the present report we describe the results from a pilot study aimed at detecting enterovirus sequence in cardiac tissues, obtained through endomyocardial biopsies, from patients suffering from cardiac diseases in the Amazon region. Six samples that were collected from three patients were analysed by RT-PCR showing 3 positive and 3 negative results. These preliminary findings suggest the participation of enteroviruses in the etiology of cardiac diseases, mainly myocarditis, and warrant further and broader local studies on this subject.