Showing papers in "The Journal of Infectious Diseases in 1974"

An Apparently New Enterovirus Isolated from Patients with Disease of the Central Nervous System

Abstract: An apparently new enterovirus was isolated in California from more than 20 patients with central nervous system (CNS) disease during the past four years; one strain was isolated from the brain of a fatal case of encephalitis. The representative BrCr strain had the physicochemical properties of an enterovirus. The human origin of the virus strains was confirmed by the reisolation from the original clinical specimens and the demonstration of increases in neutralizing antibody in patients from whom virus was isolated. Cross-neutralization and immunodiffusion tests indicated that the virus was distinct from the currently recognized enteroviruses of man. A few strains in the group were weakly pathogenic in suckling mice and produced symptoms similar to those produced by group A coxsackieviruses. A number of the strains required treatment with sodium deoxycholate to disaggregate the virus before neutralization could be demonstrated with homologous antiserum.

Comparison of Three Agents of Acute Infectious Nonbacterial Gastroenteritis by Cross-Challenge in Volunteers

Abstract: duced in volunteers with bacteria-free stool filtrates derived from each outbreak. These filtrates containing the Hawaii and Montgomery County agents, as well as filtrates containing the previously described Norwalk agent, produced clinically similar illness in volunteers. Therefore, volunteers were cross-challenged to determine whether illness was produced by antigenically related or unrelated agents. It was suggested that the Norwalk and Hawaii agents were antigenically dissimilar, since disease produced by either agent failed to confer immunity to subsequent disease caused by the other. In contrast, similar studies suggested antigenic relatedness between the Norwalk and Montgomery County agents, since Norwalkinduced disease seemed to confer immunity to later challenge with the Montgomery County agent.

Response of man to infection with Vibrio cholerae. I. Clinical, serologic, and bacteriologic responses to a known inoculum.

Abstract: The spectrum of illness and the immunologic response produced by cholera in volunteers were studied. The strains of Vibrio cholerae used were classical Inaba 569B and classical Ogawa 395. An oral dose of 108 organisms in buffered saline was required to induce the diarrhea of cholera. When given with live organisms, NaHCO3 lowered the infecting dose from 108 to 104 organisms. Clinical manifestations of infection varied from culturally positive formed stools to "rice water" diarrhea. Severe diarrhea did not have an explosive onset but rather progressively increased in volume during a 24-hr period. In 45% of cases the stool was positive for V. cholerae before the onset of diarrhea. Titers of vibriocidal antibody rose after diarrhea, peaked the second week after challenge, and rapidly fell during the next four weeks.

Haemophilus influenzae Meningitis in Infant Rats after Intranasal Inoculation

Abstract: An animal model permitting study of bacterial meningitis has been developed in infant rats by the intranasal inoculation of Haemophilus influenzae b. Seventythree percent (29 of 40) of five-day-old animals were bacteremic 48 hr after inoculation with 107 H. influenzae b; of those with bacteremia, 79% had documented meningitis. Studies with fluorescein-labeled specific antiserum suggested that bacteria were dispersed in the upper respiratory tract, penetrated the nasal mucosa, entered the systemic circulation, and spread to the meninges from the dorsal longitudinal and lateral dural sinuses. The histologic appearance of the meningitis in infant rats was similar to that reported from specimens taken at human autopsy.

Infectious leukoencephalomyelitis of young goats.

Abstract: A previously unreported afebrile, infectious leukoencephalomyelitis of oneto four-month-old dairy goats was studied. The disease was characterized by pleocytosis and posterior ataxia that progressed to complete paralysis within two weeks of onset. Dense perivenous accumulations of lymphoreticular cells in white matter and variable myelinoclasis were the essential neuropathologic lesions. These were accompanied by mild interstitial pneumonia and hyperplasia of pulmonary lymphoid tissue. Epizootiologic observations suggest that goats become infected either in utero or immediately after birth. The disease was transmitted to newborn goats by intracerebral and intraperitoneal inoculation of a 220-nm millipore filtrate of nervous tissue from a naturally infected goat. This observation and the failure to isolate bacteria or mycoplasma suggest that the causative agent is a virus, which thus far appears to be serologically unrelated to other animal viruses. The nature of the neuropathologic changes suggests that this disease may share pathogenic mechanisms with postinfectious encephalitis of man.

Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections

Abstract: The peak and trough levels of bacteriostatic and bactericidal activity of the serum and the urine of 317 patients with cancer and a bacteriologically proven infection were measured, using the patient's microorganism and the serum or urine containing the given antibiotics. When the peak titer of bacteriostatic activity in serum was > 1:8, the infection was cured in > 80% of cases. The response to therapy of patients with urinary tract infections correlated best with the inhibitory level found in the urine; clinical cure was observed in at least 90% of the patients who had a titer of bacteriostatic activity in urine > 1:4. The antibacterial activity of serum was influenced by the in vitro sensitivity of the offending microorganism, and by the composition of the antimicrobial regimen; these two factors were shown to be related to the clinical outcome. It is suggested that the determination of the antimicrobial activity of the serum, early in the course of treated infection, might allow some adjustment of antibiotic therapy. Several authors have attempted to correlate the in vitro sensitivity tests of bacteria to antibiotics and concentrations of these drugs in the serum with clinical results [1, 2]. Organisms have been considered sensitive if they can be inhibited by levels of antibiotics that are easily attained in the bloodstream after administration of the usual doses. As a result of these studies, it has been stated that therapeutic blood levels should be maintained at two to five times the in vitro MIC. One

Human Serology in Chlamydia trachomatis Infection with Microimmunofluorescence

Abstract: were from various areas of the world and from whom a TRIC-LGV organism had been isolated were tested. (All isolates had been typed and included all presently recognized immunotypes except type A.) Of the patients tested, 94% had a titer of antibody of > 1:8 against at least one of the 13 antigens used, always including the type isolated. Seventy-nine percent of sera showed a type-specific antibody response, while 15% had a pattern of multiple antibody response that precluded a specific type diagnosis. Among the 6% of patients without evident antibody, all but one were males with mild urethritis. Patients who had classical LGV infection with buboes had antibody to more than one type, often in very high titer. The possibility of rapid disappearance of microimmunofluorescent antibody after

The Enterotoxin Plasmids of Escherichia Coli

Abstract: The genetic and molecular nature of the Ent plasmids that determine enterotoxin biosynthesis in strains of Escherichia coli isolated from man and domestic animals has been investigated. At least one transmissible plasmid was present in 90% of 96 toxigenic strains compared with 36% of 204 nontoxigenic strains. Ent plasmids were demonstrated in 17% of the toxigenic strains and often appeared to be selftransmissible. A single Ent plasmid was isolated from 15 enterotoxigenic strains by conjugation experiments. The class of Ent plasmids that determines the production of both heat-stable and heat-labile enterotoxins was homogeneous and consisted of a single DNA species with an approximate molecular weight of 6.0 x 107 daltons. The class of Ent plasmids that codes for heat-stable enterotoxins only was heterogeneous and consisted of a single species of DNA that ranged in size from 2.1 to 8.0 x 107 daltons.

Induction of partial immunity to influenza by a neuraminidase-specific vaccine.

Abstract: Robert B. Couch, Julius A. Kasel,* John L. Gerin, Jerome L. Schulman, and Edwin D. Kilbourne From the Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas; the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; the Molecular Anatomy Program, Rockville Laboratory, Oak Ridge National Laboratory, Rockville, Maryland; and the Department of Microbiology, Mount Sinai School of Medicine of the City University of New York, New York, New York

Susceptibility Tests of Anaerobic Bacteria: Statistical and Clinical Considerations

Abstract: In considerations of susceptibilty testing of bacteria, linear regression has been used to relate minimal inhibitory concentration and zone size. Although lacking in statistical validity, this technique has been used for aerobic bacteria. Reports of anaerobic testing show much greater variation about the regression line; the errors of misclassification have not been analyzed. A bivariate "error rate-bounded" classification scheme is proposed for relating minimal inhibitory concentration and zone size of bacteria. This method requires the following clinical input: (1) specification of breakpoints of susceptibility as determined by minimal inhibitory concentrations and the pharmacology of the antibiotic, (2) determination of the relative importance of two types of errors, false resistant classification and false susceptible classification, and (3) determination of the acceptable rate of error of false classification. Based on this input the classification scheme determines the zone size, which gives the minimal error of misclassification with the known data on zone diameter and minimal inhibitory concentration.

Renal parenchymal accumulation of aminoglycoside antibiotics in rats.

Abstract: The half-life of gentamicin, tobramycin, kanamycin, and streptomycin, after a single subcutaneous injection, was measured in homogenates of lung, liver, and kidney in rats, and the results were compared with the half-life of these drugs in serum. Urinary excretion of antibiotics was also monitored. The half-life of the four drugs in serum and lung was approximately 30-35 min. Concentrations in the liver were regularly lower than concentrations in serum or lung. In renal tissue, gentamicin, tobramycin, and kanamycin had long half-lives of 109, 74, and 60 hr, respectively. Streptomycin, on the other hand, had a half-life of 4.6 hr. Separation of the kidneys into cortex and medulla showed that streptomycin was uniformly distributed, whereas 85% of the gentamicin, tobramycin, and kanamycin resided in the cortex. These antibiotics accumulate in the renal cortex, probably intracellularly, and have long half-lives.

Increased Rate of Carriage of Staphylococcus aureus among Narcotic Addicts

Abstract: Approximately 11% of 55 control subjects harbored the organism. The length of the interval since drug injection influenced the rate of carriage in the drug-using population. Ten percent of drug users who had not had drug injected for two weeks or more before culture carried S. aureus, in contrast to 35% of those who had had injections within one week of culture. The latter increased carriage rate was significantly different from that of the other two groups. With the increase in use of illicit drugs, the incidence of medical complications has risen. At the D.C. General Hospital alone, 8% of the 600 addicts admitted from 1967 to 1969 had bacterial endocarditis [1]. Because Staphylococcus aureus causes the vast majority of these infections, we have looked for the source of this organism. We have already reported that heroin and injection paraphernalia used by addicts were not the source of the Staphylococcus [2]. This study reports the finding of an increased carrier rate of S. aureus in parenteral drug users; the increase is related to the length of the interval since parenteral administration of drugs.

Antibodies to Epstein-Barr Virus-Associated Nuclear Antigen in Infectious Mononucleosis

Abstract: Development of antibodies to Epstein-Barr virus-associated nuclear antigen (EBNA) was studied in 72 patients with heterophil antibody-positive infectious mononucleosis. In contrast to the early response of antibodies to Epstein-Barr viral capsid antigens observed in all patients and to the D component of the Epstein-Barr virus-induced early antigens in 80% of the patients, antibodies to EBNA arose usually only one or more months after onset; in a few patients, however, these antibodies became detectable within three weeks. All patients eventually developed antibodies to EBNA. The geometric mean titer increased gradually, but even after one year it did not match that in healthy donors. After primary infections antibody to EBNA probably persists for life, since all donors with antibody to viral capsid antigen (some of them over 50 years old) showed antibody to EBNA. Conversely, no donor without antibody to viral capsid antigen had antibody to EBNA. The time of appearance of antibody to EBNA during infectious mononucleosis was unrelated to severity of illness.

Response of Man to Infection with Vibrio cholerae. II. Protection from Illness Afforded by Previous Disease and Vaccine

Abstract: Human immunity acquired after cholera or provided by cholera vaccines was evaluated. Previous diarrhea caused by infection with Vibrio cholerae induced complete protection against diarrhea after a second challenge with the homologous organism four to 12 months later; vibrios were recovered from only one of 21 patients challenged with the homologous organism. Four of six other men challenged again after the same interval with a heterologous serotype developed mild diarrhea. A whole-cell Inaba vaccine, given either parenterally or orally, produced significant protection against excretion of the organisms and lowered the incidence and severity of diarrhea; the vaccine was more effective when administered parenterally. A partially purified toxoid vaccine also provided some protection. An individual's immunity either to infection or to diarrhea was not correlated with his serum titer of vibriocidal antibody or his serum titer of antitoxin. Immunity, either naturally acquired or vaccine-induced, appeared to be directed against the vibrio rather than against the toxin. At present, cholera vaccines are less effective than previous infection in prevention of subsequent illness.

The Human Fallopian Tube: A Laboratory Model for Gonococcal Infection

Abstract: The ability of gonococci to infect the human fallopian tube in both perfusion and organ-culture systems was investigated. Scanning and transmission electron micrographs of the mucosal surface taken 3 hr after perfusion with gonococci showed microvilli adherent to the bacteria, with pili running over the membrane of the host cell. Shortly after challenge gonococci penetrated the mucosal lining to establish expanding foci of infection in the submucosal tissue. Epithelial cells were able to take up massive numbers of gonococci, and lysis of these damaged cells released numerous bacteria into the subepithelial connective tissue. Gonococci also invaded along intercellular junctions. The fact that ciliated cells, which were not invaded by gonococci, were also damaged and exfoliated raises the possibility of a diffusible cytotoxin. These ultrastructural findings are comparable to the known histopathology of acute gonorrhea. Gonorrhea is a highly infectious disease; 80% of men and women at risk from known cases develop infections [1, 2]. This high infectivity for men is remarkable when one considers that gonococci can reach the urethral mucosa only by retrograde spread and then are subjected to massive fluid flows during micturition. Less than 1 hr after intercourse, gonococci can become established on the urethral mucosa and are able to resist the flow of urine [3]. In an electron microscopic study of men with symptoms of gonorrhea of less than 24 hr duration, we showed that the ability of gonococci to anchor to the urethra can be explained by the specific attachment of gonococci to the surface of urethral cells [4]. In the acute stage of gonorrhea, gonococci and polymorphonuclear leukocytes accumulate in the subepithelial connective tissue, with associated patchy destruction of the overlying mucosa [5]. If we are to elucidate the virulence mechanisms that enable the gonococcus to attach to and subsequently to penetrate the in

Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants

Abstract: A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children. Continuing programs of surveillance during the past decade have provided evidence that viral infection is the major identifiable cause of acute lower respiratory tract disease (LRTD) in chil­ dren. Nevertheless, in every published study be­ tween one-third and two-thirds of serious illnesses cannot be associated with infection by known viruses [1-4]. When the human coronaviruses were first discovered [5-7] and were shown to be of importance in upper respiratory disease in adults [8, 9], it was hoped that they might account for a proportion of these unexplained illnesses. However, a seroepidemiologic study of their role in LRTD showed no statistically significant corre­ lation with illness [8]. Nevertheless, in the young­ est group examined (children less than one year

Microbiologic Study of Street Heroin and Injection Paraphernalia

Abstract: One hundred samples of heroin and 100 of injection paraphernalia were cultured. A wide variety of microorganisms were found. The heroin contained Bacillus species, Staphylococcus albus, fungi, Clostridium perfringens, and (rarely) gramnegative bacilli. The same organisms were recovered from the injection paraphernalia, along with a variety of gram-negative bacilli among which Escherichia coli predominated. Not one coagulase-positive Staphylococcus was isolated, despite the fact that this organism is the most common cause of infections in our addict population; thus, the addicts themselves are probably the source of Staphylococcus

Antibiotic Susceptibility Testing of Pseudomonas aeruginosa: Selection of a Control Strain and Criteria for Magnesium and Calcium Content in Media

Abstract: Because of the influence of Mg+ + and Ca+ + on the susceptibility of Pseudomonas aeruginosa to aminoglycosides and polymyxins, we studied the practical effects of variations in these cations in commercial Mueller-Hinton media. Batches of Mueller-Hinton agar sold by three firms contained 9.4-32.6 mg of Mg++ and 31.8-86.0 mg of Ca++ per liter; Mueller-Hinton broth had 2.0-5.6 mg of Mg+ + and 4.1-35.8 mg of Ca+ + per liter. Aminoglycoside MICs increased 16to 32fold with increases in Mg+ + or Ca+ + in media. Dilution tests with currently available Mueller-Hinton broth were unreliable. Disk diffusion and agar and broth dilution methods gave comparable results with media prepared to contain equivalent amounts of Mg+ + and Ca+ +. We recommend that Mueller-Hinton media contain 20-35 mg of Mg++ and 50-100 mg of Ca++ per liter. Acceptable performance of Mueller-Hinton media with a control P. aeruginosa should be assured by the manufacturer before sale and by the clinical laboratory during use.

Usage of Antibiotics in a General Hospital: Effect of Requiring Justification

Abstract: The amounts of certain antibiotics used at Boston City Hospital during recent years have been reviewed and correlated with the requirement to justify the choice of those antibiotics. This mild restraint on the prescribing of antibiotics for hospitalized patients appears to have substantially limited the use of certain potentially toxic or expensive agents, and removal of that restriction has been followed by an increase in use of those agents. Similar, relatively simple requirements may promote more effective and economical use of antibiotics and perhaps of other classes of drugs.

Effects of Tetracycline on Leukotaxis

Abstract: Tetracycline, in concentrations common during therapy, markedly depressed migration of human leukocytes in vitro. Sera from 12 of 13 volunteers who received oral tetracycline after infection with Mycoplasina pneuimoniae inhibited leukotaxis of normal leukocytes. Random migration and chemotaxis of leukocytes from two additional subjects were depressed for up to 24 hr after a single 1-g dose of tetracycline. When tetracycline was tested over a wide range of concentrations, leukotaxis was depressed by lower concentrations (0.01-10 [tg/ml) but was stimulated by higher concentrations (30-300 [ig/ml) of the antibiotic. Metabolic studies revealed that production of leukocyte lactate was elevated significantly in the presence of a high level of tetracycline. The mechanisms by which tetracycline affects leukotaxis are not known.

Effect of Tetracycline on the Phagocytic Function of Human Leukocytes

Abstract: Phagocytosis and the intracellular killing of microbes are fundamental functions of polymorphonuclear neutrophil leukocytes. Bacteriostatic antibiotics are effective only with proper neutrophil function. Thus, inhibition of leukocyte function by bacteriostatic antibiotics may have important therapeutic implications. The possibility that these functions of peripheral blood leukocytes may be effected during antimicrobial therapy has not been investigated extensively. The purpose of the present study was to extend earlier investigations into the effect of tetracycline on phagocytosis of bacteria and yeast by human neutrophils. Reports on the effect of tetracycline on the function of leukocytes have been contradictory. In 1950 an engulfment-inhibiting effect was ascribed to chloratetracycline [1]. However, in a later report by other investigators, no such effect was demonstrated with tetracycline hydrochloride [2]. In more recent reports tetracycline hydrochloride has been shown to inhibit chemotaxis [3, 4] and maximal reduction of nitroblue tetrazolium dye (NBT) [5] by human leukocytes. In one study tetracyclines were shown to inhibit the bactericidal effect of serum, but not opsonization of bacteria [6].

Immunity to Infections on Secretory Surfaces

Abstract: The field of immunology developed as attempts were made to understand the observed phenomenon that, in many cases, individuals become immune (often permanently) to an infectious disease after having had that disease. As a natural corollary of this fact, attempts were made to induce this immune state without causing illness, or at least to reduce acceptably the severity of illness. During the past 200 years, the corollary aim has probably proven more successful than the attempts to understand the phenomenon, and the development of the several immunization practices now widely used has been the most successful aspect of the disciplines of immunology and infectious disease (with the possible exception of the role of the latter in the generally improved state of public hygiene). In addition, we feel that this contribution from the combined efforts of those in the fields of infectious diseases and immunology will continue to be great, e.g., in the development of vaccines against caries, herpesvirus, and streptococcal infections, the hepatitides, gonorrhea, and syphilis, and in improved vaccines against cholera and influenza.

The Tecumseh Study of Respiratory Illness. VI. Frequency of and Relationship between Outbreaks of Coronavirus Infection

Abstract: Specimens of blood collected in Tecumseh, Michigan over a four-year period were studied for rise in antibody titer against coronavirus OC43. Peaks of infection were found in the winter and spring of 1966, 1968, and 1969; at other times, infections occurred sporadically. All age groups were involved, especially the very young. Rises in titer by CF and by HAI tests frequently did not occur together in the same individual. Agreement between the two tests was better in 1966 and 1969 than in the other years. A portion of the paired specimens showing rises in CF and/ or HAI titer was tested by neutralization. Rises in neutralizing antibody were usually found in pairs collected in 1966 and 1969 but not in those collected in 1967 and 1968. The infecting viruses in 1966 and 1969 thus appeared more closely related to OC43 than did those in 1967 and 1968.

Effect of a Toxin Produced by Haemophilus influenzae on Ciliated Respiratory Epithelium

Abstract: Tracheal organ cultures from the human fetus, the chick embryo, and several rodents were used in a study of the effect of Haemophilus influenzae on respiratory ciliated epithelial cells. H. influenzae grew in medium containing tracheal organ cultures from different sources, resulting in ciliostasis after various periods of time. Supernatant fluids of cultures of H. influenzae contained a ciliostatic substance that was active at high dilution in rat tracheal organ cultures. Cultures of human fetus and chick trachea were less sensitive, and some human fetal tracheas were insensitive. Histologic studies showed loss of cilia, damage to epithelial cells, and sloughing. The ciliostatic substance was produced early in the growth cycle of H. influenzae, was released into the medium, was nondialyzable, and was stable in heat. This substance was produced by all types and strains of H. influenzae tested. The possibility that the ciliostatic substance was an endotoxin was proposed, and the role of this substance in the pathogenesis of infections of the respiratory tract due to H. influenzae was considered.

Pathogenesis of herpetic encephalitis in mice after ophthalmic inoculation.

Abstract: The pathogenesis of herpetic encephalitis in mice after inoculation of the cornea with herpes simplex virus type I is defined. To accomplish this, assays for infectious virus and morphologic studies using standard histologic, immunofluorescent, and ultrastructural techniques were performed on appropriate tissues during the course of infection. In both the peripheral and the central nervous systems the infection spread rapidly along nerve fibers and tracts and extended more slowly by direct cell-to-cell extension. Recurrences of ophthalmic infection in mice that had previously recovered from the acute disease could not be demonstrated, although latent virus was shown to be harbored in the trigeminal ganglia of these animals. Herpes simplex virus (HSV), a ubiquitous virus in the human population [1-3], induces several disease syndromes. These range from the common and relatively benign "cold sores," to acute, lifethreatening encephalitis [4]. After primary infection, the virus establishes a unique association with its host in which recurrences of overt disease are interspersed with intervals of latency. As was first

Tropical Canine Pancytopenia: Clinical, Hematologic, and Serologic Response of Dogs to Ehrlichia canis Infection, Tetracycline Therapy, and Challenge Inoculation

Abstract: For further elucidation of the pathogenesis of tropical canine pancytopenia (TCP), 14 German shepherd dogs were evaluated following infection with Ehrlichia canis, therapy with tetracycline, and challenge inoculation. Nine dogs developed severe chronic TCP, characterized by severe pancytopenia, hemorrhage, and secondary bacterial infection. In all dogs antibody titers increased for more than 80 days after infection, and all dogs developed hypergammaglobulinemia. Prolonged and incomplete hematologic recovery followed termination of infection by tetracycline therapy in dogs with severe chronic disease. After treatment levels of serum y-globulin returned to normal. A second inoculation of treated dogs with E. canis resulted in reinfection and hypergammaglobulinemia, but with variable increases in serum antibody. Results indicate that aplastic anemia may be important in the pathogenesis of severe chronic TCP, and that increasing antibody titers and hypergammaglobulinemia reflect persistent infection with E. canis. Differences in response to challenge may reflect underlying immunologic differences between dogs with severe disease and those that do not become seriously ill.