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Biomedical subjects

C D Brandt

Publications and source records attributed to C D Brandt.

16 recordsLinked to original sources

Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes.

Polymerase chain reaction (PCR) testing using up to four primer pairs and biotinylated probes was 97.9% sensitive (188 of 192 specimens positive) and 100% specific (267 of 267 specimens negative) for detecting the presence or absence of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells from pediatric patients whose HIV status has been confirmed. SK38/39 and SK145/150 were the most sensitive primer pairs, respectively detecting HIV DNA in 95.6 and 95.9% of peripheral blood mononuclear cell specimens from HIV-infected children and collectively detecting all adequately tested PCR-positive specimens. Primer pairs SK29/30 and SK68/69 respectively detected HIV DNA in only 76.4 and 76.6% of HIV-positive specimens. Among infants born to HIV-seropositive mothers, 30 who subsequently were confirmed to be infected were sampled when they were less than or equal to 6 months of age; in all but one infant, HIV DNA was found in the first specimen collected. Among the nine youngest infected infants tested, all were PCR positive by 38 days of age. PCR methods thus have reliably detected vertically transmitted HIV infection early in life.

Acquired Immunodeficiency Syndrome

Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rate within families.

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.

Antibodies, Viral

Influenza A and B virus infection in infants and young children during the years 1957-1976.

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.

Antibodies, Viral

Comparative epidemiology of two rotavirus serotypes and other viral agents associated with pediatric gastroenteritis.

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.

Adenoviridae

Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay.

To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.

Antibodies, Viral

Human reovirus-like agent infection. Occurrence in adult contacts of pediatric patients with gastroenteritis.

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.

Adolescent

Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children.

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%).

Acute Disease

Safety and antigenicity of inactivated influenza virus vaccines in children: trials with monovalent and bivalent A/New Jersey/76 (HswN1) and A/Victoria/75 virus vaccines in Washington, D.C..

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.

Adolescent

Use of a free viral immunofluorescence assay to detect human reovirus-like agent in human stools.

Human reovirus-like agent (HRVLA) is a major cause of gastroenteritis in infants and young children in many parts of the world. Detection of HRVLA in stools is impractical with the techniques currently available. We describe a rapid immunofluorescence assay for detection of HRVLA in stools. Results with this assay agreed well with results obtained from examination of stool specimens by electron microscopy.

Animals

Human reovirus-like agent as the major pathogen associated with "winter" gastroenteritis in hospitalized infants and young children.

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.

Acute Disease

Recent advances in the aetiology of viral gastroenteritis.

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.

Animals

Cell-mediated immunity to respiratory syncytial virus induced by inactivated vaccine or by infection.

Transformation and increased mitotic activity in donor lymphocytes exposed to specific antigens is considered by many to be a manifestation of cell-mediated immunity. In attempts to understand the apparent "sensitization" of individuals to respiratory syncytial virus (RSV) as a result of receiving inactivated RSV vaccine, in vitro lymphocyte transformation studies were carried out on infants who had received inactivated RSV vaccine and on infants who had received a similarly prepared inactivated African green monkey kidney (AGMK) cell-grown parainfluenza type 1 virus vaccine or a trivalent parainfluenza vaccine prepared in hen's eggs. Each group included some infants who had, and others who had not, undergone natural RSV infection under our observation before the lymphocyte studies. Lymphocytes were studied from 21 infants and young children who had received the inactivated RSV vaccine, 14 who had received a similarly prepared inactivated parainfluenza 1 vaccine, and 5 who received a trivalent parainfluenza vaccine. Twelve of the RSV vaccinees and 14 of the parainfluenza vaccinees had been naturally infected with RSV as indicated by virus recovery and/or antibody rise between the time of vaccination and the lymphocyte studies. In comparing the arithmetic mean for RSV-specific transformation and mitotic activity there was a significant difference between RSV vaccinees and parainfluenza vaccinees whether one compared those who had undergone natural RSV infection or those who had not undergone natural infection. The difference between RSV vaccinees who had not undergone natural RSV infection and RSV-infected parainfluenza vaccinees also was significant. There was a greater level of transformation and mitotic activity in those who had experienced natural infection than those who had not among both RSV vaccinees and parainfluenza vaccinees, but these differences were not significant statistically.

Child, Preschool

Temperature-sensitive mutants of influenza A virus: response of children to the influenza A/Hong Kong/68-ts-1(E) (H3N2) and influenza A/Udorn/72-ts-1(E) (H3N2) candidate vaccine viruses and significance of immunity to neuraminidase antigen.

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.

Antibodies, Viral

Coxsackievirus B5 infection and aseptic meningitis in neonates and children.

In metropolitan Washington, DC, an outbreak of aseptic meningitis in children was recognized in the summer and fall of 1972. Age-specific attack rates were highest in children less than 1 year of age. The incidence of cases showed two peaks: one in July and another in October. Coxsackievirus B5 was associated with cases occurring in July, August, and September, but was not implicated in the October cases. Seventy-six percent of the confirmed coxsackievirus B5 infections in aseptic meningitis patients occurred in infants less than 2 months old. Specific meningeal symptoms were less frequently observed in these young infants, although viral isolations were more common (13 of 15) compared to patients over 2 months of age (four of 19). Analysis of reported coxsackievirus B5 infections in Washington, DC, and the United States as a whole suggests a five- or six-year periodicity.

Adolescent

Potential of attenuated respiratory syncytial virus vaccine for infants and children.

Respiratory syncytial virus (RSV) disease is a major cause of death and hospitalization in infancy and a frequent cause of morbidity throughout childhood. Serum antibody does not protect as is evident from the study of natural disease and use of killed vaccines. Local antibody responses occur in natural illness. Possibly serum antibody in the absence of local antibody plays a part in illness. We have studied local and serum antibody response to potential attenuated vaccines: a 26 degrees C adapted RSV and a ts mutant RSV. Both produced the desired infection as evidenced by virus recovery, serum and local antibody response. However, both appear to have had residual pathogenicity for young infants. This included mild bronchitis after the 26 degrees C RSV and mild rhinitis, which might be acceptable, but also fever and otitis in one infant after the ts RSV. Also, some of the virus recovered in the ts studies had wild type characteristics. An acceptable RSV vaccine strain will (a) infect without undergoing reversion or other genetic changes, (b) induce resistance to wild type virus, (c) cause no or very mild inflammatory changes such as the rhinitis associated with the vaccines thus far tried.

Administration, Intranasal