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Biomedical subjects

L J Anderson

Publications and source records attributed to L J Anderson.

At least 19 recordsLinked to original sources

Acute hemorrhagic conjunctivitis due to enterovirus 70 in American Samoa: serum-neutralizing antibodies and sex-specific protection.

Acute hemorrhagic conjunctivitis due to enterovirus 70 has caused extensive outbreaks in tropical areas since 1969. Between December 1, 1990, and March 4, 1991, an outbreak of acute hemorrhagic conjunctivitis due to enterovirus 70 occurred in American Samoa, where an outbreak due to the same agent had occurred in 1981. A survey of 5% of the households (134 households, 1,095 individuals) was conducted throughout the island of Tutuila. The outbreak affected 58% of the population, with age-specific attack rates greater than 50% for all age groups except children younger than 2 years. Attack rates were significantly higher for children 2-10 years old (65%) than in the remainder of the population. Women aged 21-40 years had higher rates than did men the same age (66 vs. 49%), possibly because of the close association of women and young children. At higher preepidemic titers, there was evidence of protection from clinical disease among males but not among females. Enterovirus 70 can cause large outbreaks even in a population already exposed in a previous large outbreak; protection due to previous infection is only partial.

Antibodies, Bacterial

Chronic parvovirus infection in a presumably immunologically healthy woman.

Infection due to parvovirus B19 is common and usually resolves over several weeks. Prolonged infection has been reported primarily in immunodeficient hosts. The present report describes a chronic infection in an apparently immunologically healthy woman. The illness was characterized by recurrent episodes of paresthesia without anemia. Laboratory studies demonstrated persistence of parvovirus-specific DNA for nearly 4 years.

Antibodies, Viral

Prenatal diagnosis of intrauterine infection with parvovirus B19 by the polymerase chain reaction technique.

Human parvovirus B19 is a recently recognized cause of fetal hydrops and death. Efforts to characterize the natural history of fetal infection with this virus have been hampered by the lack of sensitive and specific tests for diagnosis in utero. Using the highly sensitive polymerase chain reaction (PCR) assay, we determined the fetal infection status in 56 pregnancies by testing amniotic fluid, fetal serum, and maternal serum for B19 DNA and antibodies. Factors associated with a high risk of B19 infection were fetal disease, exposure to persons with erythema infectiosum, or signs or symptoms of acute B19 infection. Fifteen women (27%) were B19 IgM-positive, a status suggesting recent infection; the positivity of all of the corresponding fetal specimens for B19 DNA in the PCR was indicative of fetal infection. In four of these cases, serial ultrasonographic examinations documented spontaneous resolution of fetal hydrops. Twenty-four women (43%) were IgG-positive and IgM-negative; this pattern suggested prior infection. The PCR gave positive results, consistent with recent maternal infection, in four of these cases. Seventeen women (30%) were IgG-negative and IgM-negative, a pattern suggesting no prior infection; the PCR results in four cases were indicative of a possible early maternal infection or a possible atypical immune response. The PCR is a sensitive and rapid method for the diagnosis of intrauterine infection with human parvovirus B19 and promises to facilitate studies of the natural history and treatment of this infection.

Adolescent

Major trends in nosocomial viral infections.

Viruses have recently become appreciated as nosocomial pathogens. There is insufficient data to characterize trends in rates of viral nosocomial infections, but there have been major trends in methodologies and concepts. New groups of patients, such as infants and the elderly, are becoming appreciated as being at risk for serious nosocomial viral infections, whereas other groups, such as immunodeficient patients are expanding because of the epidemic of human immunodeficiency virus (HIV) infection and expanded use of immunosuppressive treatment. The continued addition of new viruses, such as HIV, human parvovirus B19, and rabies virus, to the list of potential nosocomial pathogens suggest that most human viruses can probably be serious nosocomial pathogens under the right circumstances. Advances in medical treatments and procedures, such as cadaveric dura mater grafts and laser treatment of warts, have provided new avenues for nosocomial transmission of viruses. Improved and wider availability of diagnostics promises to be a major force in improving our understanding and ability to prevent viral nosocomial infections. With these advances, viral diagnostic laboratories should become an important member of the infection control team. In parallel with trends in methodologies and concepts, there have been major advances in our understanding of ways to prevent some nosocomial viral infections. Application of these prevention measures is an important challenge to the infection control practitioner.

Cross Infection

Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions.

B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine.

Amino Acid Sequence

Human parvovirus B19 specific IgG, IgA, and IgM antibodies and DNA in serum specimens from persons with erythema infectiosum.

To determine the diagnostic use of different markers of acute parvovirus B19 infection, serum specimens obtained from 128 persons with erythema infectiosum were tested for specific immunoglobulin G (IgG), IgA, and IgM antibodies by capture enzyme immunoassay (EIA) using Chinese hamster ovary (CHO) cell-expressed B19 antigen, and tested for circulating B19 DNA by polymerase chain reaction (PCR). A significant rise in specific IgG and IgA antibodies was detected in 87% and 77%, respectively, of persons from whom acute- and convalescent-phase serum specimens were available. Specific IgA antibodies were detected in single serum specimens from 90% of cases and were present in 22 (18%) of 120 persons from a control group without a history of recent exposure to B19. Specific IgM antibodies were detected in 97% of cases and one person (1%) from the control group. B19 DNA was detected in 94% of cases and was absent in 20 persons from the control group positive for both IgG and IgA antibodies. Serum specimens obtained between 4 and 6 months after onset of illness from six additional persons were also tested. All had specific IgG antibodies, four (67%) had IgA, five (83%) had IgM, and none had detectable B19 DNA. Our data indicate that 1) specific IgA antibodies are too persistent to be a useful indicator of recent B19 infection; 2) specific IgM antibodies are the most sensitive indicator of acute B19 infection in immunologically normal persons but can persist up to 6 months; and 3) B19 DNA can often be detected up to 2 months after onset of illness even in immunologically normal hosts and might be a useful adjunct test for diagnosis of acute B19 infection.

Adolescent

Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus.

Monoclonal antibodies to the hemagglutinin protein, fusion protein, phosphoprotein, matrix protein, and nucleoprotein of measles virus were evaluated as detector antibodies in capture enzyme immunoassays (EIAs) for the detection of specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to measles virus. A pool of monoclonal antibodies to hemagglutinin protein and nucleoprotein proved optimal and was further evaluated. Specific IgM was detected in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of clinical measles cases and vaccinees, in 26% of healthy persons, and in 36% of infants 8 months postvaccination; consequently, IgA antibodies were not a useful indicator of recent measles infection. A significant increase in IgG antibodies between paired specimens was detected in 92% of clinical cases and all vaccinees. Only 59% of infant specimens had persistent IgG antibodies as detected by capture EIA at 8 months postvaccination, whereas all specimens had antibodies as detected by hemagglutination inhibition and plaque neutralization. An alternative indirect EIA, in which antigen was directly absorbed to the solid phase, was more sensitive than the capture design, detecting IgG antibodies in all infants postvaccination. When standardized with a microneutralization assay for the detection of persistent antibodies, the indirect IgG EIA gave predictive values for positive and negative tests exceeding 90%. Our capture IgM and indirect IgG EIAs provide a practical combination of serologic tests for the determination of acute measles virus infection and past exposure to measles virus or vaccine, respectively.

Antibodies, Monoclonal

Genetic diversity of the attachment protein of subgroup B respiratory syncytial viruses.

Respiratory syncytial (RS) virus causes repeated infections throughout life. Between the two main antigenic subgroups of RS virus, there is antigenic variation in the attachment protein G. The antigenic differences between the subgroups appear to play a role in allowing repeated infections to occur. Antigenic differences also occur within subgroups; however, neither the extent of these differences nor their contributions to repeat infections are known. We report a molecular analysis of the extent of diversity within the subgroup B RS virus attachment protein genes of viruses isolated from children over a 30-year period. Amino acid sequence differences as high as 12% were observed in the ectodomains of the G proteins among the isolates, whereas the cytoplasmic and transmembrane domains were highly conserved. The changes in the G-protein ectodomain were localized to two areas on either side of a highly conserved region surrounding four cysteine residues. Strikingly, single-amino-acid coding changes generated by substitution mutations were not the only means by which change occurred. Changes also occurred by (i) substitutions that changed the available termination codons, resulting in proteins of various lengths, and (ii) a mutation introduced by a single nucleotide deletion and subsequent nucleotide insertion, which caused a shift in the open reading frame of the protein in comparison to the other G genes analyzed. Fifty-one percent of the G-gene nucleotide changes observed among the isolates resulted in amino acid coding changes in the G protein, indicating a selective pressure for change. Maximum-parsimony analysis demonstrated that distinct evolutionary lineages existed. These data show that sequence diversity exists among the G proteins within the subgroup B RS viruses, and this diversity may be important in the immunobiology of the RS viruses.

Amino Acid Sequence

Antibody enhancement of respiratory syncytial virus stimulation of leukotriene production by a macrophagelike cell line.

The clinical and epidemiologic features of respiratory syncytial virus (RSV) infections suggest that RSV-specific antibody may sometimes contribute to the disease process. Recently, it has been demonstrated that virus-specific antibody can enhance RSV infection of macrophagelike cells in vitro. We evaluated the possibility that antibody might also enhance RSV stimulation of the bronchoactive mediator of inflammation leukotriene C-4 (LTC4)in a macrophagelike cell line, U937. The addition of RSV led to little increase in LTC4 production, but addition of RSV plus anti-RSV antibody increased production to a level similar to that achieved with calcium ionophore, a known stimulator of LTC4 production. The antibody-enhanced increase in LTC4 production occurred rapidly (within 15 min), peaked at 60 min, and achieved levels 1.5- to 3.0-fold above that for cells or cells plus virus. RSV plus anti-RSV antibodies in the form of polyclonal serum, monoclonal antibodies, or F(ab')2 fragments and parainfluenza virus types 1 and 3 plus their respective antibodies all increased LTC4 levels over that for the virus alone. These results demonstrate that antibody plus the corresponding virus or protein can increase leukotriene production. This phenomenon could contribute to diseases, such as RSV bronchiolitis, that appear to be caused by an interaction between the virus (or antigen) and host immunity.

Antibodies, Viral

Pharyngoconjunctival fever caused by adenovirus type 4: report of a swimming pool-related outbreak with recovery of virus from pool water.

During the summer of 1977, an outbreak of pharyngoconjunctival fever (PCF) occurred at a private recreational facility in Georgia. A total of 72 cases of PCF was identified. Adenovirus type 4 (AV-4) was recovered from conjunctival or pharyngeal swab specimens from 20 of 26 persons in the group of cases tested. AV-4 was also recovered, for the first time reported in the literature, from two concentrated samples of water obtained from the swimming pool at the facility on different dates. All persons affected had had direct or indirect contact with the pool. A linear relation between the amount of time spent in the water and the attack rate was demonstrated (r = 0.929, P less than 0.01). Investigation showed that inadequate amounts of chlorine had been added to the pool water. Frequently, levels of free chlorine were below the recommended level of 0.4 mg/liter. Breakpoint chlorination and closing of the pool for the summer stopped the spread of PCF.

Adenoviridae Infections