Biomedical subjects
Publications and source records attributed to A J Bednarz-Prashad.
Rotaviruses have proven to be major causes of pediatric diarrheal disease morbidity and mortality worldwide. The past several years have yielded substantial new insights into these viruses, their epidemiology, and the mechanisms of host resistance to them. These insights have in turn resulted in development of several candidate rotavirus vaccine strains, bringing closer the possibility of effective protection of young children from rotavirus disease.
Accurate diagnosis of rotavirus is important in both clinical and research situations. A total of 100 stool specimens from children with diarrhea were tested for rotavirus by electron microscopy. These specimens were then coded and tested for rotavirus by four procedures: a monoclonal antibody-based enzyme immunoassay (EIA) (Pathfinder; Kallestad Laboratories, Inc., Austin, Tex.), two polyclonal antibody-based EIAs (Rotazyme II; Abbott Laboratories, North Chicago, Ill.; and an EIA performed with reagents from the National Institutes of Health, Bethesda, Md. [NIH reagent EIA]), and a latex agglutination (LA) assay (Rotalex; Medical Technology Corp., Somerset, N.J.). The sensitivity of the monoclonal antibody EIA (95%) was superior to those of the polyclonal antibody EIAs (73% for Rotazyme II and 57% for the NIH reagent EIA) and the LA assay (61%). The specificity of the LA assay (98%) was slightly better than those of the other systems (88 to 96%). The positive and negative predictive values of the monoclonal antibody EIA (93 and 96%, respectively) were better than those of Rotazyme II (82 and 80%, respectively), the LA assay (96 and 76%, respectively), and the NIH reagent EIA (93 and 74%, respectively). The visual readings of the monoclonal antibody EIA correlated better with the spectrophotometric optical density readings than did the visual readings of the polyclonal antibody EIAs; however, the agreement of both with electron microscopy results was poor when 1+ or plus-minus readings were observed. The monoclonal antibody EIA is more sensitive and predictive than other rotavirus detection systems and second only to the LA assay in specificity in detecting rotavirus in stool specimens.
Rotavirus particles are unique in their configuration. They have a double-shelled protein capsid, inside which are the viral RNA fragments and a viral polymerase. The outer shell is involved in the infectivity of the virus particle; without it the particle is not infective. At the cellular level during the infection process, this outer shell is made permeable by an unknown mechanism. This makes the RNA polymerase within the particle accessible to precursors of new RNA. Transcription begins, and progeny virus RNA and protein soon accumulate in the cell. In vitro studies show that chelators such as EDTA and EGTA may be used to make the virion permeable, allowing the measurement of viral RNA polymerase activity. These chelators remove divalent cations such as Ca++ from the virus particle, thereby altering the outer shell of the virus [2]. We were interested in measuring the effect on rotavirus of chelators that have been used to treat diarrheal disease, such as clioquinol, an 8-hydroxyquinoline derivative and the principal ingredient of Entero-Vioform (Ciba Pharmaceutical Co, Summit, NJ). Seven of 10 three-day-old Icr white mice simultaneously inoculated with EDIM and administered a single dose of clioquinol developed diarrhea 48 hr after inoculation, although none had displayed diarrhea at 24 hr. These mice, therefore, developed diarrhea 24 hr later than six of eight untreated animals (P = 0.004 at 24 hr by Fisher's exact test). Moreover, no animals receiving doses of clioquinol every 12 hr had developed diarrhea by 48 hr after inoculation (P = 0.006 at 24 hr and P = 0.0001 at 48 hr, compared to untreated mice).(ABSTRACT TRUNCATED AT 250 WORDS)
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