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Biomedical subjects

D O Matson

Publications and source records attributed to D O Matson.

At least 73 records · Page 4Linked to original sources

Recent developments with human caliciviruses.

Caliciviruses (CVs) are human and animal pathogens. The best known human CVs are Norwalk virus (NV) and Snow Mountain agent. Recent molecular studies have confirmed that CVs are a unique taxonomic family. These molecular studies also have clarified relationships among previously poorly characterized human enteric viruses, led to new diagnostic tests and identified potential relationships between human and animal CVs. The purpose of this review was to describe these recent developments.

Animals↗

Viral gastroenteritis in day-care settings: epidemiology and new developments.

Viral gastroenteritis is one of the most frequently encountered problems in the day-care setting. Four different viruses are proven diarrhea pathogens, and each consists of multiple antigenic types. Most vial gastroenteritis cases occur during outbreaks, indicating that exposure is high once the agent is in the center. The occurrence of frequent outbreaks of infection in DCCs permits better studies of the immunologic factors that protect children against infection in this setting than can be achieved outside group settings.

Adenoviridae↗

Fecal antibody responses to symptomatic and asymptomatic rotavirus infections.

The role of anti-rotavirus fecal IgA (RVflgA) in protecting children against natural rotavirus infections is unclear. Rotavirus outbreaks occurred in each of four day care centers attended by 129 children; 42% of the infections were asymptomatic. RVflgA titers were measured by EIA before infection and 4 weeks later in 50 children who excreted rotavirus (excretors) and in two samples 4 weeks apart from 50 children without detected virus excretion (nonexcretors). Forty-three (86%) excretors and 18 (36%) nonexcretors had a fourfold or greater RVflgA titer rise. Preexposure RVflgA titers were higher in not infected than symptomatic (P = .002), asymptomatic than symptomatic (P = .036), and not infected than asymptomatic children (P = .07). RVflgA titers after asymptomatic infections were slightly than after symptomatic infections (P = .087). In summary, higher RVflgA titers were associated with protection against infection and illness and increased fourfold or more in both asymptomatic and symptomatic children.

Age Factors↗

Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination.

A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%).

Adolescent↗

Costs associated with office visits for diarrhea in infants and toddlers.

We determined costs associated with diarrhea in a < 36-month-old ambulatory population. Children with acute diarrhea were enrolled during the rotavirus season at three centers. Questionnaires to assess costs of both medical and nonmedical factors were administered at the enrollment visit and 1 week later. Office computer records were reviewed to identify all visits by children with diarrhea during 1 year. Fifty-one patients were enrolled. The average cost per episode of diarrhea was $289, which included: $144, missed work; $57, office visits; $23, laboratory tests; $21, medications; $18, changed diet/oral rehydration solutions; $15, travel; $7, extra diapers; and $6, extra child care. During 1 year diarrhea accounted for 4% of all visits and 10% of visits among those < 36 months old. The annual cost at the three centers was $346,000, which extrapolates to $0.6 to $1.0 billion for the United States. Twenty-one percent of this cost was attributable to rotavirus diarrhea. We conclude that outpatient care for pediatric diarrhea is a major health care cost in the United States.

Child, Preschool↗

Extraintestinal rotavirus infections in children with immunodeficiency.

Some rotavirus strains, including vaccine candidates, have been demonstrated to cause hepatitis in immunodeficient and malnourished mice and to grow in human liver cells. To determine whether rotavirus spreads outside the intestine in naturally infected children, we examined tissues from four immunodeficient children affected with severe combined immunodeficiency disease, acquired immunodeficiency disease syndrome, or DiGeorge syndrome. Chronic rotavirus-related diarrhea, which persisted until death, had also developed in each child. Using indirect immunoperoxidase techniques, we identified rotavirus antigen in the liver and kidney with a hyperimmune guinea pig antiserum prepared to double-shelled rotavirus particles. Similar immunostaining with an antiserum to a rotavirus nonstructural protein (NS26) provided evidence of active virus replication. The observed reactivity was eliminated specifically when serial sections were immunostained with the same antiserum that had been absorbed with either double-shelled rotavirus particles or NS26. Immunostaining was not observed in the liver of children with other diseases (alpha 1-antitrypsin deficiency, inspissated bile syndrome, and acute rejection of a transplanted liver). These findings demonstrate that rotavirus infections in children can extend beyond the intestinal tract. Further studies are warranted to determine whether extraintestinal rotavirus replication occurs in children without severe immunodeficiency, such as malnourished children.

Acquired Immunodeficiency Syndrome↗

Outbreaks of human enteric adenovirus types 40 and 41 in Houston day care centers.

OBJECTIVE: Human enteric adenovirus (EAd) types 40 and 41 cause diarrhea in young children, but little is known about their association with outbreaks of diarrhea in the child care setting. This study evaluated EAd as a cause of outbreaks of diarrhea among infants and toddlers in day care centers. DESIGN: Stool specimens were collected weekly regardless of symptoms during four periods from January 1986 to April 1991, from children 6 to 24 months of age enrolled in prospective studies of diarrhea in day care centers. All diarrhea stool specimens were tested for bacterial enteropathogens, rotavirus, and Giardia lamblia. A total of 131 outbreaks occurred during the study. No etiologic agent was identified in 77 outbreaks. Stool specimens from 75 of these 77 outbreaks and from another 21 outbreaks of diarrhea with a known cause were evaluated for EAd with a monoclonal antibody-based enzyme immunoassay. RESULTS: A total of 4402 stool specimens from 613 children from these 96 outbreaks was tested for EAd. The virus was detected in specimens collected during 10 outbreaks, 3 of which occurred in 1986, 3 in 1988, 1 in 1989, 1 in 1990, and 2 in 1991. Of 249 children, 94 (38%) in these 10 EAd outbreaks were infected with EAd. In 51 children (54%) the infection was symptomatic and in 43 (46%) it was asymptomatic. Outbreaks lasted 7 to 44 days (mean 24.5 days). Duration of EAd excretion ranged from 1 to 14 days (mean 3.9 days), with excretion occurring from 7 days (mean 2.6) before diarrhea began to 11 days (mean 5.3 days) after diarrhea stopped. CONCLUSION: Enteric adenovirus types 40 and 41 are an important cause of outbreaks of diarrhea among children attending day care centers, often involve children in more than one room, and frequently produce asymptomatic infection.

Adenovirus Infections, Human↗

Comparisons of rotavirus VP7-typing monoclonal antibodies by competition binding assay.

Three sets of neutralizing monoclonal antibodies (MAbs) used to type the outer capsid protein VP7 of four group A rotavirus serotypes (1 through 4) were compared in competition immunoassays. Reciprocal competition was observed for each of the VP7 type 2-, 3-, and 4-specific MAbs. The VP7 type 1 MAbs exhibited variable competition patterns with other VP7 type 1 MAbs. MAb RV4:3, which has been used to recognize antigenic variants within VP7 type 1 strains, showed reciprocal competition with the four VP7 type 3 MAbs (RV3:1, YO-1E2, 4F8, and 159) using a VP7 type 3 virus (SA11) as antigen. MAb 2C9, also prepared against VP7 type 1, reacted with VP7 type 3 strains and competed with a VP7 type 3 MAb, 159, using RRV as antigen. Use of the different sets of VP7 type-specific MAbs in the enzyme-linked immunosorbent assay permitted the recognition of six antigenic variants within VP7 types 1, 2, and 3 among specimens whose VP7 type could not be determined previously with only one set of typing MAbs. These results demonstrate differences of typing ability among these VP7-specific MAbs and emphasize the need to improve the sensitivity of typing systems by incorporating panels of MAbs reacting with several neutralizing epitopes.

Antibodies, Monoclonal↗

Characterization of serum antibody responses to natural rotavirus infections in children by VP7-specific epitope-blocking assays.

Knowledge of the immune response to rotavirus is crucial for vaccine development. We compared an epitope-blocking assay (EBA) that uses VP7-specific monoclonal antibodies with neutralization assays (NAs) with polyclonal antisera for detecting serum antibody responses after natural rotavirus infection in children. Twenty-six serum pairs from children living in an orphanage with and without symptoms during two rotavirus outbreaks were evaluated for VP7 type 1-, 2-, 3-, and 4-specific antibody responses. In the first outbreak, which was caused by a VP7 type 3 strain, homotypic antibody responses were detected in 11 of 11 symptomatic children by NA and in 10 of 11 symptomatic children by EBA. Heterotypic antibody responses were detected more frequently (12 of 15 children) by NA than by EBA, and the heterotypic epitope-blocking antibody responses occurred in children older than 14 months of age. Antibody responses in asymptomatic children were more commonly detected by EBA than by NA. EBA results from the sera of children in the second outbreak indicated that it was caused by VP7 type 4, whereas NA results suggested it was caused by VP7 type 3. Our results confirm that EBA is a sensitive and specific method for determining VP7 type-specific immune responses after natural rotavirus infections.

Antibodies, Viral↗

Comparative growth of different rotavirus strains in differentiated cells (MA104, HepG2, and CaCo-2).

The production of viral antigen after infection of MA104, HepG2 (derived from human liver), and CaCo-2 (derived from human colon) cells with various cultivatable human and animal rotavirus strains was compared using immunofluorescence tests. All rotavirus strains examined expressed antigen in CaCo-2 cells and MA104 cells, but only some virus strains, namely, SA11-Cl3 (simian), RRV (simian), CU-1 (canine), and Ty1 (turkey), produced antigen in numbers of infected HepG2 cells comparable to infections in MA104 and CaCo-2 cells. Fl-14 (equine), OSU (porcine), NCDV (bovine), and Ch2 (chicken) strains were found to infect moderate numbers of HepG2 cells. Most human rotaviruses (representing viruses in serotypes 1, 2, 3, 4, 8, and 9), a simian rotavirus variant (SA11-4F), lapine (Ala, C-11 and R-2) viruses and porcine (Gottfried) virus infections resulted either in no detectable antigen or antigen synthesis in a low percentage of HepG2 cells. Human rotavirus isolates obtained from the stool specimens of an immunocompromised child with rotavirus antigen in his liver showed two different patterns of replication in HepG2 cells. Examination of the replication of a subset of viruses in the liver and intestinal tissues of orally infected suckling mice showed the CU-1 and Ty1 strains replicated well, while the OSU and human rotavirus strains did not. These results indicate that growth restriction in HepG2 cells is not serotype-specific, and growth of a virus in HepG2 cells does not necessarily correlate with the hepatotropic potential of a virus strain. Factors that may influence these differences of virus infectivity in HepG2 cells are discussed.

Animals↗

Serotyping of human rotaviruses in Argentina by ELISA with monoclonal antibodies.

Human rotaviruses are the major, recognized cause of infantile diarrhea worldwide. Characterization of naturally occurring human isolates indicates that there are six human rotavirus serotypes, four of which (serotype 1 to 4) are widespread. We utilized monoclonal antibodies specific for the VP of serotypes 1, 2, 3, and 4 as capture antibody in a sandwich enzyme-linked immunosorbent to serotype rotaviruses directly in stool samples. The stool samples were collected from 1983 through 1986, from two epidemiologic studies in the area of Buenos Aires, Argentina. All four serotypes assayed were found Serotype 2 and 3 viruses, which were detected most frequently in 1983 and 1984, were virtually undetected in 1985 and 1986 (chi 2 = 23, P = less than 0.001 for this difference). No significant difference was noted among the three collection sites for serotype prevalence. These results indicate that the changing predominance of rotavirus serotype in a given region can involve multiple serotypes at the same time. Analysis of an outbreak of diarrhea in two neighboring families which occurred during a prospective study of community diarrhea documented inter- and intra-family spread of one serotype of virus.

Antibodies, Monoclonal↗

Impact of rotavirus infection at a large pediatric hospital.

Information is limited about national patterns of rotavirus infection throughout the USA. Discharge records and laboratory rotavirus detection for 1979-1989 at the Texas Children's Hospital, Houston, were evaluated to determine the impact of rotavirus gastroenteritis at a large children's hospital. The availability since 1983 of diagnostic assays less expensive than electron microscopy was associated with increased rotavirus detection. Only 67% of rotavirus-positive samples came from children likely to have had community-acquired acute gastroenteritis. Combined laboratory results and ICD-9 discharge diagnosis codes (008.6, 008.8, and 558.9) measured rotavirus activity better than either alone. A case definition for hospitalization for rotavirus infection resulted in an estimate that an average of 473 children were hospitalized for rotavirus infection at Texas Children's Hospital each year over the 10-year period. These cases accounted for 3.0% of all hospital days and $1.5 million per year in bed costs at this hospital. Hospitalization rates and the impact of hospital costs for the USA were estimated by extrapolation.

Acute Disease↗

Serotype variation of human group A rotaviruses in two regions of the USA.

The first longitudinal study of group A rotavirus serotype distribution in the USA is reported. ELISAs incorporating neutralizing monoclonal antibodies specific for the VP7 protein of serotypes 1, 2, 3, and 4 were used to determine the antigenic variation of group A rotaviruses in two collections of stool specimens. Stool samples were collected from children hospitalized during 1979-1989 at Texas Children's Hospital, Houston, and from children from a more rural population hospitalized during 1981-1989 in the north-central USA. The predominant serotype varied from year to year in Houston, with serotypes 1, 3, and 4 each predominant in 1 or more years. In the north-central population only serotype 1 was predominant each year. Within a single rotavirus season in the Houston area, serotypes were not equally distributed by week of the season or county of residence. These differences in the distribution of serotypes have broad implications for the design and interpretation of vaccine programs.

Age Factors↗

Molecular epidemiology of rotavirus in children attending day care centers in Houston.

Serotype distribution of group A rotavirus in children attending day care centers has not been previously reported. Fifteen centers in Houston participated in longitudinal monitoring of rotavirus infection during one to three consecutive rotavirus seasons. Monitoring included daily recording of the presence of diarrhea and weekly stool collection. Stool specimens containing rotavirus were analyzed by a monoclonal antibody (MAb)-based ELISA specific for the VP7 protein of serotypes 1, 2, 3, and 4 and by gel electrophoresis. A total of 318 children had 362 rotavirus episodes; 149 could be serotyped. Serotype distribution of this population was similar to that of children hospitalized for diarrhea in a large pediatric hospital in Houston during the same period. Symptomatic infections were predominantly due to serotype 1 rotaviruses in season 2 and serotype 3 rotaviruses in season 3. Episodes recurred in 43 children; 2 children had second symptomatic infections of the same serotype as the first. Electrophoretic differences among rotaviruses of a same serotype were common and more frequent among serotype 1 than serotype 3 viruses.

Age Factors↗

Asymptomatic human calicivirus infection in a day care center.

Human caliciviruses (HCVs) are little known, recently recognized viruses associated with gastroenteritis. We identified HCV infection in an outbreak of gastroenteritis which occurred in one room of a day care center (DCC) participating in a longitudinal study of diarrhea. Utilizing an enzyme-linked immunoassay and immunosorbent electron microscopy to detect HCV, we tested specimens from all children in attendance during the period of the illness outbreak and during prior and subsequent weeks. HCV infection was documented in 14 children, 11 of whom were asymptomatic. Thirteen of the 14 HCV-infected children were 8 months of age or younger. New cases of HCV infection occurred during a 4-week period. Forty percent of children less than 1 year of age were infected with HCV during the period of investigation. Few documented HCV infections have been reported. This may be related to a high attack rate of predominantly asymptomatic infections in early life, resulting in a high prevalence of antibody to HCV by 4 years of age.

Caliciviridae↗

Porcine rotaviruses antigenically related to human rotavirus serotypes 1 and 2.

Fecal samples from rotavirus-infected piglets were characterized by a serotyping enzyme-linked immunosorbent assay (ELISA) by using monoclonal antibodies (MAbs) specific to human serotypes 1, 2, 3, and 4 (D. O. Matson, M. K. Estes, J. W. Burns, H. B. Greenberg, K. Taniguchi, and S. Urasawa, submitted for publication). Rotavirus in 19 of 25 specimens tested from two herds of pigs from Buenos Aires province, Argentina, were classified antigenically as follows: one serotype 1, four serotype 2, two serotype 3, and no serotype 4. Six specimens reacted with both serotype 1 and 2 MAbs, and viruses in six specimens probably belonged to other serotypes because they reacted only with a VP7 common epitope MAb. Two porcine rotavirus fecal samples found to contain both serotype 1 and 2 viruses by the MAb-based test and one found to contain a serotype 2 virus were grown in tissue culture. When plaque-purified preparations of these tissue culture-adapted viruses were analyzed in the serotyping ELISA, the C60 and C86 preparations reacted only as serotype 1 viruses, indicating that the original fecal samples, which showed multiple VP7 reactivities, were heterogeneous and apparently contained two types of viruses. Testing of plaque-purified C134 virus confirmed its serotype 2 reactivity. The MAb-based serotype designations of these viruses also were confirmed by using a neutralization immunoperoxidase focus reduction assay. This is the first report of the occurrence of serotype 1 and 2 rotaviruses in animals. The MAbs originally developed to serotype human rotaviruses can be utilized to type animal rotaviruses.

Animals↗

Human calicivirus-associated diarrhea in children attending day care centers.

We investigated human calicivirus (HCV)-associated diarrhea in children attending day care centers by using stool specimens collected in 1981-1983. We used a screening enzyme-linked immunosorbent assay (ELISA) derived from reagents prepared against the Sapporo strain of HCV and confirmed positive results with a blocking ELISA and immunosorbent electron microscopy. HCV was detected in 11 (2.9%) of 375 diarrheal stools and in none of 86 stools from asymptomatic contacts. This incidence rate was half that noted for rotaviruses and higher than that noted for Campylobacter, Salmonella, and Shigella in the original study. HCV was found in stool specimens from children in nine day care centers; HCV-associated diarrhea was sporadic, occurred with greater frequency in young children, and had a summer-fall predominance. Our results indicate that HCV is an important cause of diarrhea in day care centers and that frozen stool samples can yield epidemiological data on HCV infection.

Arizona↗