Diarrhea-associated adenovirus from the respiratory tract.
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Biomedical subjects
Publications and source records attributed to J O Arrobio.
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Infants and young children with rotavirus (RV) or visualized adenovirus in their stools were tested for the simultaneous presence of a respiratory viral pathogen in their upper respiratory tract. Overall, at least 10.7% of 484 study subjects had such dual infections, including 8.3% of 385 RV-positive gastroenteritis patients and 24.3% of 37 RV-positive respiratory disease patients. Respiratory syncytial virus was present in 34.1% of 41 dual infections with RV and at least 40% of the 12 to 15 dual infections with visualized fecal adenovirus. Other pathogens found in the respiratory tract of patients with RV or visualized fecal adenovirus infections included influenza viruses, adenoviruses, parainfluenza viruses, rhinoviruses, and a cytomegalovirus.
Adenoviruses were found in 8.6% of 900 pediatric inpatients with diarrhea who were tested by electron microscopy of a fecal specimen and cell culture inoculation of a throat swab and an anal swab specimen. In 5.1% of these patients, including 13.5% of patients who were four through five months of age, adenovirus particles were visualized in the fecal specimen. Controlled study demonstrated that visualized adenoviruses, especially those that did not grow readily in conventional Hep-2 cell cultures, were significantly associated with diarrhea. About 80% of the visualized adenoviruses from patients with diarrhea or vomiting or both, including 94% of the viruses that grew in the 293 cell line but that did not grow readily in Hep-2 cultures, proved to be enteral adenoviruses--adenoviruses from either group F (type 40) or group G (type 41). Inpatients with gastroenteritis and confirmed enteral adenoviruses ranged in age from one through 16 months, with a median age of seven months. Enteral adenoviruses apparently are endemic in this locale, as one or more of these viruses have been found in every calendar month for nine successive years.
The quantity of adenoviruses in a diarrhea stool provided a strong presumptive indication of the presence or absence of an adenovirus from subgenus F or G (proposed species 40 or 41). These adenoviruses were found in the stools of 91% of 56 acutely ill diarrhea patients with one or more than one adenovirus particle per min of direct electron microscopic viewing, as compared with 40% of 20 acutely ill diarrhea patients with less than one detected adenovirus particle per min of viewing.
During the period January 1974 through July 1982, fecal samples from 1,537 pediatric inpatients with gastroenteritis were tested for enteric viruses by electron microscopic and rotavirus enzyme-linked immunosorbent assay techniques. Rotaviruses were detected in 34.5% of these patients, enteric adenoviruses were detected in 4.7%, approximately 27-nm viruses were detected in 1.6%, and at least one of these agents was found in 40.1% of the study subjects. Three infections were by an apparently new agent which morphologically is a rotavirus, but which failed to react in the rotavirus enzyme-linked immunosorbent assay. During the first 8 calendar years of study, rotaviruses were detected in 39.0% of 577 patients in the even-numbered years and 30.3% of 702 patients in the odd-numbered years. Adenoviruses were found in all calendar months. Rotaviruses were found in inpatients in November through July, whereas approximately 27-nm viruses were found in October through June. The percentage of patients who had a demonstrated viral infection rose steadily from 7.4% in September to 72.0% in January and then steadily declined to 2.9% in August. Viral infection was especially common in study subjects who were 7 through 24 months of age; 61% of such children had one or more enteric viruses. Rotavirus-infected patients tended to be younger during the months of greatest rotavirus activity than at the beginning and end of the rotavirus season, presumably because of a greater exposure to virus at the height of the rotavirus outbreak.
Specimens containing respiratory tract epithelial cells from infants and children with acute respiratory disease were evaluated by using an indirect immunofluorescence technique with two specific respiratory syncytial virus monoclonal antibodies. One (RS/HN 13-1) was directed against a cell surface viral antigen, and the other (RS/HN 25-2) was directed against viral antigen present in large cytoplasmic inclusions. The same results on presence or absence of respiratory syncytial virus were obtained by cell culture and immunofluorescence in 93% of 252 patients tested adequately by both methods. The sensitivity of indirect immunofluorescence was approximately equal to that of cell culture. A total of 84 specimens were positive for RSV by immunofluorescence; 82 of them were positive with both monoclones, and the remaining 2 were positive only with the monoclone directed against the internal protein. The fluorescence pattern of the latter monoclone was unique and easily recognized. Indirect immunofluorescence testing with monoclonal antibodies to respiratory syncytial virus proved to be a very useful diagnostic technique, and results could be obtained within 4 h of specimen collection.
During 5.5 years of a study in Washington, D.C., hospitalizations of children for rotavirus gastroenteritis tended to be more common after a month of cold or dry weather than after a corresponding calendar month of warm or wet weather. Overall, there were 84% more (178 versus 97) inpatients with rotavirus gastroenteritis after a set of relatively colder individual months taken as a group than after an equal number of warmer corresponding calendar months taken as a group. Comparable differences were not seen with nonrotavirus gastroenteritis patients. There also were 45% more rotavirus hospitalizations after the set of months with the least depth of precipitation compared with the set of corresponding calendar months with the greatest depth of precipitation. Rotavirus infection in young infants, the children least likely to be directly exposed to outdoor conditions, showed some of the most marked weather-associated effects. These findings suggest that weather-related low indoor relative humidity and indoor crowding may be key factors in the epidemiology of rotavirus disease.
An approximate 10% suspension in water of the first available stool sample from 411 infants and young children with acute gastroenteritis was examined by electron microscopy (EM) after 2 min of negative staining. This procedure enabled the detection of 88% of the 199 rotavirus infections, all of the 22 adenovirus infections, and 47% of the 15 approximately 27-nm virus infections ultimately detected by a combination of techniques, including immune electron microscopy (IEM) and rotavirus enzyme-linked immunosorbent assay (ELISA). Of the 204 infections detected by direct EM of stools, 76% were detected within 2 min of viewing, and 94% were detected within 6 min of viewing. Type 1 and type 2 rotavirus particles were visualized with approximately equal efficiency, although type 2 rotavirus infections were more common. Rectal swab preparations were clearly inferior to stool preparations for the detection of virus infection by direct EM. IEM examination was required for efficient visualization of viruses in rectal swab specimens. ELISA was the most sensitive method for the detection of rotaviruses; with this method, all infections in which rotavirus particles were visualized by EM or IEM were detected. However, 73% of the 1,834 specimens which were presumptively positive for rotavirus by conventional indirect ELISA proved to be falsely positive on the basis of EM, IEM, blocking ELISA, confirmatory ELISA, or a combination of these methods. False-positive rotavirus ELISA reactions apparently were eliminated when fecal specimens were tested in a modified confirmatory ELISA with a lower dilution of rotavirus-negative (pre-immunization) than rotavirus-positive (post-immunization) capture antibody from the same animal.
A sharp outbreak of gastroenteritis associated with human rotavirus type 2 involved not only all of nine infants and young children in a playgroup but also seven of 10 parents and grandparents studied. The source of the outbreak appeared to be two non-playgroup siblings. Six of 11 individuals studied shed human rotavirus type 2, and each of seven from whom paired sera were obtained developed a type 2 sero-response. Overall, evidence of infection with rotavirus type 2 was demonstrated in 10 of 11 individuals by detection of virus in stools and/or a serologic response in an enzyme-linked immunosorbent assay.
Influenza A virus activity was demonstrated in infants and young children from metropolitan Washington, DC during each of 19 successive August-July respiratory disease years, and during 17 of these years at least 2% of hospitalized respiratory disease patients yielded an influenza A or B virus and/or showed an influenza A or B serum complement-fixing (CF) antibody response. Between October 1957 and July 1976, 14.3% of 860 croup patients and 5.3% of a total of 5655 hospitalized respiratory patients, including croup patients, showed evidence of influenza A or B infection. The mean period of hospitalization with either virus was about 8 days, though serious infection with influenza A virus was 4.5 times more common than with influenza B virus. Both influenza viruses were detected more frequently in respiratory disease outpatients than in respiratory disease inpatients. Patients with serious influenza A virus infections were especially likely to have croup (particularly during the H3N2 era), to be seen during December through February, and to be black male infants. During the peak month of a composite of 13 consecutive influenza A virus outbreaks, influenza A virus infection was demonstrated in 67.6% of croup patients and in 35.6% of all hospitalized respiratory patients including croup patients. During the peak month of a composite of 6 consecutive influenza B virus outbreaks, influenza B virus infection was demonstrated in 36.0% of croup patients and in 10.8% of all hospitalized respiratory disease patients including croup patients.
Human rotavirus (HRV) type 1 or 2, adenovirus, or non-cultivatable 27 nm virus-like particles were demonstrated by electron microscopy and/or rotavirus ELISA in fecal samples from 45.5% of 604 gastroenteritis inpatients, 25.0% of 200 gastroenteritis outpatients and 6.0% of 812 control subjects, all sampled at Children's Hospital National Medical Center. Washington, DC. Rotaviruses were the most common pathogens detected as 39% and 22% of gastroenteritis inpatients and outpatients, respectively, shed HRV. About three-fourths of the rotaviruses were type 2, which was prevalent during five successive epidemic years from January, 1974, through June, 1978. HRV type 1 was detected in the last four successive epidemic years and represented nearly half of the HRV infections observed among gastroenteritis inpatients during the year 1977--1978. Both rotavirus serotypes were detected most often in the month of January, when 71% of 123 gastroenteritis inpatients and 62% of 34 gastroenteritis outpatients shed one of these viruses. Uncultivatable adenoviruses were detected significantly more frequently in stools from patients with gastroenteritis (3.9%) than from control subjects (0.6%), suggesting that these viruses played a role in acute enteric disease. The frequency of detection of 27 nm particles was not significantly different in gastroenteritis and control patients. Numerically, HRV infection was detected most often in gastroenteritis inpatients who were 10 through 12 months of age. The group of gastroenteritis inpatients with the highest percentage of HRV infection was 13 through 15 months of age. The excess of type 2 HRV infection relative to type 1 infection was especially large in those aged 7 through 24 months. Lower socioeconomic status or greater crowding appeared to be associated with the occurrence of rotavirus infection earlier in life and earlier in the epidemic year.
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Sixty-four adult family contacts of 61 young patients with gastroenteritis were included in a study for evidence of concurrent infection with the human reovirus-like agent (HRVLA) of infantile diarrhea. Evidence of infection was detected in 26 (41%) of the adult contacts. The HRVLA infection occurred significantly more often among adult contacts of pediatric patients infected with HRVLA (55%) than among contacts of young patients not infected with the agent (17%). Mild cases of gastroenteritis developed in only three of the contacts infected with HRVLA.
Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).
Safety and antigenicity of monovalent and bivalent A/New Jersey/NJ)/76 (HssN1) and A/Victoria/75 inactivated influenza virus vaccines were studied in 125 children aged three to 18 years. In recruitment, families who knew the study team, who were professionally involved, and/or who were under close continuing care were more likely to volunteer for such studies than those who were unfamiliar with the team or institution. Antibody responses and systemic reactions occurred more often after administration of inactivated whole-virus vaccine than after split-virus vaccine. Significant titers (greater than or equal to 1:40) of hemagglutination-inhibiting antibody to A/NJ/76 virus occurred in 95% of normal children three to 18 years of age who received two doses of the same vaccine (whole or split). However, insufficient numbers of children achieved a reasonable antibody titer (greater than or equal to 1:40) after one dose of vaccine.
We found a human reovirus-like agent in the stools of 42 per cent of 143 infants and young children hospitalized with acute gastroenteritis between January, 1974, and June, 1975. Half the patients studied by electron microscopy and serologic technics had evidence of infection with the agent. The infection had a seasonal pattern: 59 per cent of those admitted during the cooler months (November to April) shed the agent, with a peak of 78 per cent in December, 1974, and January, 1975, combined. None of the patients admitted during the warmer months (May to October) shed the agent. None of 275 Escherichia coli isolates from 32 patients with diarrhea produced heat-labile enterotoxin, whereas 17 of the 32 had evidence of infection with the reovirus-like agent. In addition, 14 of 40 parents of 37 patients with diarrhea associated with the reovirus-like agent were also infected, but most infectious were inapparent. This agent appears to be the major cause of diarrheal illness in the young during the cooler months.
Studies with the human reovirus-like (HRVL) agnet, also designated rotavirus and duovirus, have revealed that it is a major aetiological agent of diarrhoea of infants and young children in many parts of the world. In a study of patients admitted with a diarrhoeal illness to the Children's Hospital of the District of Columbia in the United States from January 1974 to June 1975, it was found that half of the patients studied by both virus shedding (by electron microscopy) and serological (complement-fixation) techniques demonstrated evidence of infection with the HRVL agent. The temporal distribution of infections with the HRVL agent followed a seasonal pattern with this agent being shed exclusively by patients admitted during the cooler months of the year. Electron microscopic examination of stools was as efficient as serological methods for detecting infection with the HRVL agent. We also initiated studies to determine the possible mode of transmission of the HRVL agent by studying contacts of hospitalized patients. We found that 35% parents of patients with HRVL infections were also infected with the HRVL agent. Serological studies revealed that the HRVL agent was antigenically related to the Nebraska Calf Diarrhoea Virus, the epizootic diarrhoea of infant mice virus, the SA-11 virus, and the "O" agent.
One of two slightly different influenza A/ts-1[E] recombinant candidate live vaccines was given intranasally to each of 23 young children. Twelve of 15 children who had no serum HI antibody but who did have serum ANAB at the time of administration became infected and 1 had mild rhinitis. All eight who lacked both types of antibody became infected and they shed virus in higher titer and for longer than the former group; five had rhinorrhea and five had mild fever. These findings suggest that serum ANAB plays a part in modulating influenza virus infection and that the full expression of virulence of these or other attenuated influenza vaccines may be manifest only in individuals lacking both HI antibody and ANAB. These particular candidate vaccine strains appear to be attenuated for older children (who have some prior experience with influenza A as demonstrated by serum ANAB), but the occurrence of fever in over half who had no prior experience indicates that they would not be acceptable for a vaccine in wide-spread use.