Priorities in infection control: the impact of new technology.
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Biomedical subjects
Publications and source records attributed to W Schaffner.
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A prevalence serosurvey was performed on an 11.7% sample of the 6,503 adult male inmates in Tennessee prisons. On the basis of the sample, 0.9% of the prisoners possessed hepatitis B surface antigen, and 29.5% had one or more serum markers for hepatitis B virus (HBV). Thirty-two possible risk factors were analyzed for association with possession of HBV serum markers. The significant risk factors for possession of HBV markers in this population were found to be age, intravenous drug use while not incarcerated, intravenous drug use while incarcerated, race, education, military service history, and duration of prior and current imprisonments, in that order of importance. Given the modest contribution of incarceration to overall risk, mass immunization of prisoners against HBV seems unwarranted. Prisoners with unusually long sentences or who use intravenous drugs in prison are subgroups at particularly high risk. The logistic model can be used to target a serological screening and immunization program.
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A patient with the acquired immunodeficiency syndrome was found to have a continuous bacillemia of Mycobacterium avium-intracellulare by examination of Kinyoun-stained buffy coat smears. There were 29 cells/cu mm that contained acid-fast bacilli (AFB) and 1.5 X 10(5) AFB/ml of whole blood. The cells of the reticuloendothelial system were engorged with AFB, suggesting reticuloendothelial saturation. The peripheral blood involvement and magnitude of the mycobacterial burden are analogous to leprosy, and it is suggested that other similarities between the immunobiology of leprosy and disseminated M avium-intracellulare infection in the acquired immunodeficiency syndrome may exist.
We conducted a statewide controlled trial of three methods to improve antibiotic prescribing in office practice: a mailed brochure, a drug educator visit, and a physician visit. Educational topics were three antibiotics contraindicated for office practice and oral cephalosporins. Medicaid prescribing data were used to select donors who needed education. The effect of the methods was evaluated by comparing the change in prescribing (the year before the intervention v the year after the intervention) for the doctors receiving education with the prescribing of comparable doctors chosen as controls. The mailed brochure had no detectable effect, and the drug educator had only a modest effect. The physician visits produced strong attributable reductions in prescribing of both drug classes. For the contraindicated antibiotics, the reductions were 18% in number of doctors prescribing, 44% in number of patients per doctor receiving these drugs, and 54% in number of prescriptions written per doctor. For the oral cephalosporins, both number of patients and number of prescriptions per doctor were reduced by 21%. Doctors responded equally well to recommendations designed to improve the quality of care and to reduce the cost of care.
Transcriptional enhancers, originally discovered in viral genomes, are short, cis-acting, regulatory sequences that strongly stimulate transcription from promoters of nearby genes. We demonstrate the existence of an enhancer within a mouse immunoglobulin heavy chain gene. A DNA fragment located between the joining region and the switch recombination region in the intron upstream of the immunoglobulin mu constant region has been linked, in both orientations, to genes coding for rabbit beta-globin or SV40 T antigen. This element enhances the number of correct beta-globin gene transcripts by at least two orders of magnitude and also stimulates production of T antigen. It acts from several hundred to several thousand base pairs up or downstream of a promoter without amplifying template copy number. Of the various cell lines tested, the immunoglobulin gene enhancer functions only in lymphocyte-derived (myeloma) cells. We propose that this tissue-specific enhancer contributes to the activation of somatically rearranged immunoglobulin variable region genes and possibly to abnormal expression of other genes (e.g. c-myc) that become translocated to its domain of influence.
Cells infected or transformed by adenovirus-2 express complexes of the viral E19 protein and class I transplantation antigens. To eliminate the complication of the numerous metabolic changes in adenovirus-infected and -transformed cells, we detached the E19 gene from its viral background by constructing transient expression vectors where the E19 coding sequence is flanked by the SV40 early promoter and the 3' region of the rabbit beta-globulin gene. E19 production was assayed 2 days after transfection of monkey COS or human HeLa cells with vector DNA. Efficient E19 gene expression depends on the presence of an intron (the second beta-globin intron), and the E19 protein is properly processed and anchored in the plasma membrane of transfected cells. The vector-synthesized E19 protein is also associated with class I transplantation antigens in human cells, since a fraction of it is coprecipitated both with antiserum against HLA antigens and with monoclonal antibodies against beta 2-microglobulin.
An outbreak of Norwalk agent gastroenteritis occurred in a chronic-care hospital in Tennessee in April 1981. Fifty-five per cent of the elderly psychiatric patients and 61 per cent of the nursing employees on one floor became ill. Infection was most likely to have spread from patient-to-patient by nursing employees. Certain chronic medications seemed to protect patients from symptomatic infection. Anticholinergic drugs appeared to mask the symptoms of this disease; psyllium ('Metamucil') may have prevented infection in some patients. We suggest that prospective studies be undertaken to confirm the possible value of psyllium in averting infection with Norwalk agent.
Multiresistant Klebsiella pneumoniae has been endemic among adult patients at Vanderbilt University Medical Center since 1973. Multiresistant K. pneumoniae was absent from pediatric wards until 1979, when it produced an epidemic in the intensive care nursery followed a year later by a second epidemic involving K. pneumoniae of the same serotype. The 105 megadalton (Md) conjugative resistance (R) plasmid (pCER7999) transferring multiple antibiotic resistance in the adult, endemic strain was found also in isolates from the first epidemic in the intensive care nursery. The mother of a child in the nursery harbored E. coli containing the same 105 Md R plasmid. The second epidemic also involved a 105 Md conjugative R plasmid, which, however, by molecular analysis was different from the first epidemic plasmid and also pCER7999. Thus, the second epidemic resulted from the introduction of a new, unrelated multiresistant K. pneumoniae strain. Contemporary hospital epidemiology often requires the application of molecular techniques for an understanding of nosocomial infections.
We have obtained correct transcripts from the mouse immunoglobulin lambda I light chain gene on transfection into human HeLa cells. Linkage to simian virus 40 (SV40) DNA containing a transcriptional "enhancer" element was required to raise lambda-chain gene transcription to a detectable level in our transient-expression assay. The transcripts had the same 5' end as authentic lambda I mRNA when the SV40 enhancer element was 150 base pairs upstream from the cap site. The situation was different when the lambda-chain gene promoter was separated from the SV40 sequences by more than 1 kilobase pair of spacer DNA; then, lambda-chain gene transcripts were not correctly initiated in human HeLa, monkey CV-1, and mouse 3T6 cells. In this respect, the lambda-chain gene behaves differently from the rabbit beta-globin gene, which can be activated by the SV40 enhancer over distances of several kilobases.
The potential for anticholinergic toxicity due to concurrent use of medications was assessed among 5,902 continuous nursing home residents and a comparable group of ambulatory patients. During the study year nearly 60% of the nursing home residents and 23% of the ambulatory patients received drugs with anticholinergic properties. Based on recommended doses of the drugs, 565 of the nursing home patients and 413 of the ambulatory patients could have received three or more anticholinergic medications concurrently. An examination of nursing home patients receiving the most frequently prescribed antipsychotic and tricyclic antidepressant drugs concurrently revealed that physicians did not choose drugs selectively within the two classes in order to minimize the potential for anticholinergic toxicity. The findings of this study suggest that the risk of anticholinergic toxicity may be underestimated by physicians.
During a 31-month period in 1979-1981, nine patients at a renal transplant center in Tennessee developed invasive infections with Aspergillus species. Despite an extensive search, no common environmental source of contamination was found. A matched case-control study of host risk factors showed that leukopenia, prior administration of antibiotics, and treatment with azathioprine and antilymphocyte serum were not significantly related to the development of aspergillosis. In contrast, the administration of high-dose corticosteroids posed a significant risk. An average daily dose of greater than or equal to 1.25 mg of prednisone/kg per day for the entire interval studied was the best predictor of subsequent invasive infection with Aspergillus.
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In April 1981, an outbreak of hepatitis A occurred among state legislators in Tennessee. Although the number of cases was small, we traced the source to a food handler who served cold meats and cheese. This investigation demonstrates the value of rapid serologic testing using a radioimmunoassay technique and matched case-control analysis to identify small foodborne outbreaks of hepatitis A.
Transcriptional "enhancers" have been identified in both the monkey virus SV40 and in the mouse polyoma virus. Here we report that these enhancers show a cell type preference. This was done, (i) by assaying for T antigen expression and viral DNA replication of polyoma DNA which contains its own enhancer or the enhancer of SV40 virus, and (ii) by linking either of the two enhancer elements to the rabbit beta 1-globin gene and measuring transient globin expression in mouse and primate cells. The results were consistent in all the assays: In mouse cells the polyoma enhancer is slightly more effective than the SV40 enhancer. However, in primate cells the SV40 enhancer induces a four to six fold higher level of gene expression than does the polyoma enhancer.
Thirty-eight cases of toxic shock syndrome were reported in Tennessee between January 1, 1979, and March 31, 1981. Thirty-one of these cases (82%) occurred in white women less than 30 years of age; none occurred in black women. We suspected that age and racial differences in tampon use could contribute to the relatively high risk of toxic shock syndrome in young white women. In March, 1981, we surveyed 1,136 Tennessee women regarding their past and current used of tampons. Age and race were related, not only to whether or not tampons were used but to the way tampons were used. "Continuous" tampon use during the most recent menstrual period was most common among young white women (61%), less common among older white women (42%), and least common among black women (23%). On the other hand, the brands, absorbency types, numbers, and usage patterns did not vary greatly with respect to age or race. Comparing each woman's tampon habits in March, 1981, with her usual habits in June, 1980, suggested a striking effect of publicity about the toxic shock syndrome. We estimate that 23% to 39% of the women surveyed changed their tampon habits in an attempt to reduce their risk of toxic shock syndrome.
An outbreak of nosocomial varicella was traced to airborne spread from an immunocompromised child hospitalized from Nov 11-19, 1980. Seventy potentially susceptible children were hospitalized on the ward during that period. Although the index patient remained in strict room isolation throughout his hospital stay, eight of these patients contracted varicella. The afternoon of November 12 was the period of highest risk for acquiring varicella. Eight of 36 patients (22%) present that afternoon, compared to none of 34 patients not present that afternoon, acquired the infection. A patient's risk of contracting varicella was significantly related to how near he/she came to the index patient's room that afternoon. Airflow studies, using the tracer gas, sulfur hexafluoride (SF6), demonstrated that patient rooms on this ward were at positive pressure with respect to the corridor. Despite isolation procedures, SF6 released in the index patient's room achieved concentrations in the corridor as high as 10% of those inside the room. Airborne spread of varicella has rarely been reported, but it may be a common mode of transmission in hospitals. We suggest that patients hospitalized with varicella be placed in strict isolation in negative-pressure rooms to reduce the risk of nosocomial transmission.
The hemoglobin beta-1 gene of the rabbit was linked to a 244 bp DNA fragment from the beginning of the polyoma virus late region, not including the viral origin of replication. After transfection of such recombinant DNAs into mouse 3T6 and human HeLa cells, the polyoma sequences were found to strongly enhance the level of correct beta-globin gene transcripts over a distance of at least 1400 bp. These findings are similar to those obtained with a segment of DNA from the corresponding region of the SV40 genome (J. Banerji, S. Rusconi and W. Schaffner, 1981, Cell, in press) which, however, shows very limited sequence homology to the polyoma 244 bp segment. Using the same assay, a complete copy of polyoma virus DNA was found to interfere with the enhancement of globin gene expression in a cell type-specific manner which may be due to incorrect transcription. In contrast to the complete polyoma virus genome, the 244 bp DNA fragment will be particularly useful as a component of mammalian expression vectors since it almost exclusively yielded high levels of correct beta-globin gene transcripts.