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SummaryHemagglutination by Newcastle disease virus (NDV) is markedly affected by temperature. At room temperature the reaction is difficult to read, especially with low dilutions of virus. At 4°C the reaction is easily read and titration end-points are readily determined.At 4°C NDV appears to be adsorbed more completely by and to elute less rapidly from chicken red cells than at room temperature.Details of satisfactory methods for titration of virus and antibodies against it are presented. Both tests are carried out at 4°C.

Gastrointestinal signs and symptoms have rarely been reported in association with cytomegalovirus (CMV) infection in young infants. However, in 1981 clear pathologic evidence was presented implicating this virus as a cause of hypoganglionosis and bowel dysmotility. We report our experience with four infants with CMV infection in whom gastrointestinal dysfunction was the reason for emergency abdominal operation. Since the association was made retrospectively, we were unable to demonstrate hypoganglionosis, but our experience underscores the need to include CMV intestinal infection in the differential diagnosis of the acute surgical abdomen in young infants.

The current state of knowledge of lung defenses has been reviewed. First, mechanical factors such as aerodynamic filtration and mucociliary transport were considered. Then, in general terms, the contributions of alveolar macrophages, neutrophils, lymphocytes, and immunoglobulins, and the roles of complement, antiproteases, lysozyme, and fibronectin were examined. Interactions between these components may regulate their effect. Finally, the responses to five specific micro-organisms were reviewed to illustrate different aspects of the lung's defenses. Streptococcus pneumoniae was selected as a representative extracellular bacterial pathogen, Mycobacterium tuberculosis as an intracellular bacterial pathogen, Mycoplasma pneumoniae because it elicits significant humoral and cell-mediated immunity, respiratory syncytial virus as an example of a local viral pathogen, and measles as a viral pathogen that causes generalized disease. It was shown that these responses may not always be beneficial for the host. For each of the five infections, recommendations for improving the outcome were made.

During an eight month period in 1978, a large number of infants in a special care nursery at Bellevue Hospital, New York City, were found to carry a Staphylococcus aureus which was resistant to gentamicin. The records of 43 newborn infants who were admitted during this period of high prevalence were analyzed retrospectively for factors that might favor acquisition of gentamicin sensitive or resistant strains. It was found that neither sex nor administration of gentamicin or kanamycin played a significant role. Duration of stay was a major determinant of colonization, but there was no significant difference between the median stay of infants colonized with gentamicin sensitive or resistant strains. A life table analysis showed no difference in the rate at which gentamicin sensitive or resistant strains were acquired. As a group, staphylococci were acquired at the same rate as Gram negative rods and less rapidly than S. epidermidis. A review of all nosocomial staphylococcal infections recognized in the unit during 1977 and 1978 did not support a concern that there might be greater risk of serious infections during the months when gentamicin resistant strains of S. aureus were prevalent. Both sensitive and resistant strains appeared to be similar in virulence. Indeed, in this infant population, there were no differences in behavior between gentamicin resistant and sensitive strains of S. aureus.

SUMMARY Table 2 lists the names, abbreviations, and principle underlying most of the rapid diagnostic techniques we have described. Table 3 lists the pathogens most likely to cause lower respiratory tract infections in pediatric patients, the specimens needed for each rapid diagnostic test now generally available, and the approximate time required for its actual performance. For maximal cost-effectiveness, it is recommended that laboratory diagnosis be pursued in a stepwise manner: 1) The usual patient with acute respiratory illness who is to be managed as an outpatient may need little if any laboratory evaluation. 2) For the child for whom hospital admission is being considered, serum C-reactive protein screen, urine bacterial antigen tests, and a cold agglutinin test (at the appropriate age) will help to classify the etiology of the infection as likely or unlikely to be bacterial. If antibiotic therapy is to be given, a blood culture should be obtained before starting. 3) For the child admitted to the hospital with a possible chlamydial or viral lower respiratory infection for whom specific therapy is considered, nasopharyngeal secretions should be examined for Chlamydia and for antigens of respiratory syncytial, parainfluenza, and influenza viruses to help select the appropriate antimicrobial. Serum for IgM level may be helpful. 4) For the child who has been intubated for respiratory support, a specimen of deep respiratory secretions should be sent for Gram stain, bacterial culture, for Chlamydia, and viral antigens and culture. 5) For patients presenting with atypical symptoms, signs, or clinical course additional diagnostic possibilities should be considered and appropriate tests done even if results may not be available within 48 hours.

SummaryIt is shown that the inhibitor present in allantoic fluid for hemagglutination by and absorption of mumps virus is more active when human erythrocytes rather than when chicken red blood cells are used. It appears that the species of erythrocyte present influences the reaction between mumps virus and inhibitor in the direction of more or less combined (non-hemagglutinating) virus. A similar influence, though to a less striking degree, is also shown for the red blood cell in the influenza virus-inhibitor reaction.

Summary The case history is presented of a 4-year-old boy who, following a short period of diarrhea, developed arthritis, conjunctivitis, and urethritis. Recovery from this syndrome, which was originally described by Reiter, was accompanied by a gradual decline in S. flexner agglutinins from a level of 1 1,280 to 1 40. The significance of this observation is not clear. Attempts to recover a pathogenic microorganism, pleuropneumonia-like organism, or a virus from the joint fluids, urethral discharge, and conjunctival smears were unsuccessful.

Summary Comparative studies of pathogenicity and antigenicity were made of four strains of herpes simplex in order to investigate some of the differences which may exist between strains of a single viral species. Mice, rabbits, guinea pigs, white rats, hamsters, cotton rats and chick embryos were observed after inoculation of mouse brain emulsions by various routes. Although herpes simplex is a pantropic virus, differences between strains are accentuated by certain tests. Thus, death of the majority of animals following corneal infection of the rabbit or intranasal inoculation of the cotton rat can be used to indicate strains with prominent neurotropic tendencies, while marked local reactions after intradermal injection of the guinea pig are indicative of dermatotropism. These distinctions probably hold only for the particular species of animals and routes tested, as the strain which was most dermatotropic in our laboratory, “O”, was the cause of fatal encephalitis in a human being. It is not known whether these differences in potentiality of herpes strains are of epidemiologic significance. The development of neutralizing antibodies in rabbits after corneal and intra-abdominal inoculations was studied. Significant levels of antibody were present by three weeks and peak titers were attained by six weeks. The serologic relationships were investigated by testing the corneal reactivity of immunized rabbits to homologous and heterologous strains and by cross neutralization tests in mice and chick embryos. The chick embryo tests were found to be the most sensitive and satisfactory for this purpose.

SummaryIn vitro tests of the susceptibility of 30 normal human fibroblast lines to infection by herpes hominis, adenovirus-7, echovirus-11 and measles viruses have shown significant variations in individual host susceptibility to infection by one or more of these agents. Resistance of an individual cell line to a given virus appears to be specific for that virus, and is not necessarily associated with resistance of the same cells to other viruses.Family studies utilizing fibroblasts obtained from parents and from siblings geno-typed for the HL-A system and other biological markers suggest that, if susceptibility to viral infection in man is determined by a host cell genome, this type of genetic control may be of a multigenic nature. No pattern of dominant inheritance has been observed in the limited studies reported here. The results suggest, however, the possibility that the host's HL-A genotype or genes closely linked to the HL-A chromosomal region may play a role in conditioning resistance to viral inf...

Summary The virus of vaccinia may be cultivated for at least 3 weeks in roller-tube cultures of mononuclear cells obtained from the circulating blood of the rabbit. Following inoculation of the virus, the addition of homologous antiserum to this system does not bring about permanent inactivation of the virus. Mixtures of antiserum and virus giving no reaction in the rabbit's skin give rise to an infection of these mononuclear cells. The infection is maintained even if further amounts of antisera are subsequently added to the culture. The addition of 1 or 2 hemolytic units of complement in the form of fresh normal rabbit-serum does not enhance the effectiveness of the antiserum. In cultures of mononuclear cells, the virus does not increase as rapidly nor reach as high a titer as in cultures consisting principally of fibroblasts. In cultures of mononuclear blood-cells, complement and antiserum appeared to be more effective in temporarily suppressing the activity of the virus than in cultures consisting principally of fibroblasts. The possible application of these observatins in vitro to the dissemination of virus through the animal body and to the maintenance of latent infections is discussed.

Summary Complement-fixation tests with an egg-yolk-grown lymphopathia venereum antigen (“Lygranum CF”-Squibb) were performed on sera from patients with atypical pneumonia and from individuals with known exposure to venereal infection. The results were compared with those obtained with sera from patients with upper respiratory infections and influenza and from normal individuals. All tests included egg-yolk control antigens and Kolmer complement-fixation tests for syphilis. A modified micro Kolmer technic was used in testing with the “Lygranum CF” antigen which was comparable in sensitivity to the method recommended by the Squibb workers. There were 98 “controls,” 102 atypical pneumonia patients and 126 venereally exposed individuals who had satisfactory tests. Complete fixation with a serum dilution of at least 1 to 5 was found, respectively, in 28.6, 28.4 and 39 per cent of each of these groups. There was no correlation between the Kolmer serological test for syphilis and the “Lygranum” complement-fixation test. However, in the venereally exposed group there was a considerable number of patients whose serum reacted with the egg control antigen. Most of these showed positive Kolmer reactions. This phenomenon impairs the diagnostic value of the test among patients with venereal diseases. Twice as many atypical pneumonia as control sera reacted with the normal egg antigen. This observation is discussed. Quantitative titrations on a number of the positive sera from each group failed to reveal any clear-cut differentiation. However, quantitative study of more than one specimen of sera from each of 11 patients with respiratory infections revealed that 7 had a change in titer with progression of their disease. In 2, there was a rise in titer and in 5, a fall. In 4 of these 5, the first specimen to be examined was drawn after the second week of illness. Cutaneous and complement-fixation tests with “Lygranum” were performed on 77 venereally exposed patients. The serological test appeared more sensitive, though there were a few instances in which the cutaneous test was positive when complement fixation was negative.

An intradermal test with formalin-inactivated egg-grown mumps virus was done on 109 household contacts of 42 cases of epidemic parotitis. Sixty of these individuals were skin-test positive and 49 negative. There were 12 contact cases of epidemic parotitis and 11 of them occurred among the nonreactors. There were 27 children who gave negative skin tests and they furnished 10 of the contact cases. The possible significance of this has been discussed. The various types of reactions encountered have been described and the frequent occurrence of relatively faint reactions in children noted. The validity of the test was supported by an obvious correlation with the incidence of secondary cases, past history and the fact that patients who were originally skin-test negative were positive several months later. It is concluded that the test is of value in determining susceptibility to epidemic parotitis. In view of the large number of clinically inapparent cases, the skin test should prove most useful in practice in removing unnecessary concern for infection by parents who do not recall having had the disease.

Staphylococcal hemagglutinating antibodies are present in both 7S and 19S fractions of serum. Newly born infants receive only 7S hemagglutinins from their mothers, and this passively acquired antibody soon disappears from the circulation. Infants under 4 months of age fail to respond to severe staphylococcal infections with hemagglutinin production. Infants over 4 months of age do make hemagglutinins, but these antibodies are mostly in the 19S class. Infants and children over 4 months of age may have high titers of hemagglutinins even without a history of staphylococcal infections. Most adults have significant staphylococcal hemagglutinin titers. The distribution of staphylococcal hemagglutinating antibodies between 7S and 195 is consistent. Under the age of 16 years, most of the actively acquired hemagglutinin is in the 19S class. After 16, 7S hemagglutinins may dominate. Thus, under the conditions of natural exposure to staphylococci, age of the individual is a significant determinant of the class of his staphylococcal hemaglutinating antibodies. Although it is clear from this and other reported studies that individuals react to different antigenic stimuli by making different classes of antibodies, the biological and clinical significance of these observations are not yet completely understood.

Summary Serial specimens of sera obtained during the acute and early convalescent phases of illness from 8 individuals with clinical mumps were studied for the appearance of specific antibodies. The tests employed were complement fixation with soluble and viral antigens, agglutination-inhibition, and agglutination of human erythrocytes modified by treatment with mumps virus (Burnet test). The individual variations were marked. Nevertheless, in 6 of the 8 patients a complement fixing antibody was the first to be detected, and after 2 weeks all of the 8 patients reacted positively in 2 or more of the tests. There was no correlation in titer nor time of appearance of the complement fixing, agglutination-inhibiting nor modified cell agglutinating factors. It is therefore suggested that these represent distinct and independent responses to infection with the virus of mumps. Addendum. Since this manuscript was submitted for publication a paper on this same subject by Aikawa and Meiklejohn has appeared. (Aikawa, J. K. and Meikeljohn, G., 1949; The serological diagnosis of mumps. A comparative study of three methods. J. Immunol. 62, 261–270.) These authors also found the three tests studied by us to be valid indicators of the presence of antibody to the mumps virus.

Two newborn infants who had shared a nursery for 36 hours presented within 1 week of each other with generalized listeriosis. Since multiple cases among nursery mates are infrequent, these two cases are described in detail. The circumstances surrounding them are compared with those in two published reports of small nursery outbreaks. Together they support the possibility of an occasional newborn to newborn spread of L. monocytogenes. Review of the information which is pertinent for man suggests that, although the epidemiology of most instances of listeriosis is still unknown, it is a disease which needs to be considered more often by pediatricians.

A review of the immunology of rubella and the basic requirements of various laboratory tests used in its diagnosis.

After one week of nonspecific symptoms, pneumonia and an extremely tender and enlarged cervical lymph node developed in a 12-year-old girl who lived in an area of New Mexico known to have plague-infected rodents. Cultures from an aspirate of the node, her sputum, and blood all showed growth of Yersinia pestis. She was treated successfully with aminoglycosides and tetracycline. As the pneumonia resolved, areas of consolidation were replaced by cavitary lesions.

Summary and Conclusions Analysis of 68 sera from infants under 6 months of age showed that although 31 of 34 newborns had detectable mumps complement fixing (CF) antibodies, the serum from only 1 infant over 44 days of age gave a positive CF reaction. The rate of disappearance of mumps complement fixing (CF) and agglutination-inhibiting (A-I) antibodies was followed in 4 infants, and although there was considerable variation, the average time of disappearance for both antibodies was surprisingly similar—53 and 45 days respectively. Since placenta-passing mumps antibodies as determined in this study disappear from the circulation rather early in life, one must look to other factors to account for the rarity of mumps in infancy.

ConclusionsAt 37°C viable cells and vaccinia virus can be demonstrated in cultures composed of Tyrode's solution and chick embryonic tissue during about 4 weeks following inoculation. These results are contrasted with those previously obtained in roller tube cultures where survival of both cells and virus persists much longer and the multiplication of the virus is greatly increased.

Varicella-zoster virus (VZV), one of the most common highly communicable agents of disease, stimulates aggressive infection control measures. In a 1-year period, at one hospital, at least 93 inpatients (82 adult patients, 11 pediatric patients) and 2 hospital staff with active varicella-zoster infections served as potential sources of nosocomial infection. Six incidents of exposure to the virus that occurred without the protection of standard infection control precautions were investigated by the infection control surveillance team. One hundred fifty-six patients and 353 hospital staff were exposed. Fifty-one patients had no history of varicella-zoster infection, but only five were susceptible by serologic testing. One hundred one staff members had no history of varicella-zoster, but only 11 were susceptible by serologic testing. These exposures resulted in three secondary varicella-zoster infections, six courses of varicella-zoster immune globulin prophylaxis and furlough of 13 staff members. Epidemiologic investigation consumed approximately 356 hours of staff time, and management of exposed persons cost approximately $41,500. Prospective knowledge of the immune status of health care workers would vastly decrease the time and effort required to control hospital VZV exposures.

Surveillance of bacteremic patients within one week of the detection of a positive blood culture provides information of great clinical utility for relatively little effort. In this report one year's experience is reviewed to illustrate that an individual hospital's experience with bacteremia may diverge from national norms. Such reviews may also detect recurring errors in medical judgment which may be corrected through proper education.

Results with a VZV skin test as a marker of past infection were compared with histories of chicken pox and specific antibody detected by ELISA in 100 individuals—25 of whom were pediatric patients with malignant diseases. A negative or uncertain history was not reliable, neither were the skin test results among the oncology patients. However, among the normal individuals, the skin test when compared with the ELISA had a sensitivity of 85%, a specificity of 100%, and a positive predictive value of 100%.

Nonspecific enhancers of resistance may include (1) viral interference, (2) interferon, (3) interferon inducers, (4) bacterial interference, (5) bacterial products such as Coley's "toxins," endotoxins, or staphylococcal, BCG, and Corynebacterium parvum vaccines, (6) transfer factor, and (7) well-defined chemicals such as dinitrochlorbenzene, levamisole, and vitamin C. These are discussed only as they have been applied to man to learn whether or not they have enhanced his ability to resist infections and growth of tumors. Preliminary studies suggest that a variety of relatively safe and effective nonspecific enhancers may soon be available for clinical use.

Summary 1. A small, relatively mild outbreak of diarrhea associated with Pseudomonas aeruginosa (Bacillus pyocyaneus) occurring on an infants' ward is described. 2. The clinical course of five patients is given together with an account of the therapy employed. On the basis of encouraging results in one patient and reports of in vitro sensitivity of the organism, it is suggested that when other forms of chemotherapy fail, Polymyxin B be tried by the oral route. 3. It is shown that washing a contaminated object in soap and water does not reduce the Ps. aeruginosa count, while soaking in 70 per cent ethyl alcohol for 2 minutes is effective. It is recommended that this procedure be included in the hospital technic for prevention of cross infections. 4. Among twelve strains of Ps. aeruginosa studied for flagella antigens there were at least four serologic groups. The strains recovered from four of the five patients with diarrhea were serologically homologous and identical with the strain recovered from the hands of one of the nurses. The sole exception was the first patient whose organism was in a serologic group of its own. 5. The sera of convalescing infants did not contain agglutinins for their homologous organism. Nevertheless some adult sera taken at random had agglutinins in moderately high titer for one of the strains associated with the diarrhea.

SummaryQuantitative data are presented to show that both the mumps viral complement fixing and agglutination-inhibiting antibodies are transmitted from mother to child without any significant loss in titer. In contrast, titrations for streptococcus MG agglutinins show in most of the instances at least a 4-fold diminution of the maternal titer in the cord blood. There was no difference in results when specimens were from premature or full term infants.

Introduction Urinary sediment has been recognized for a long time as a useful parameter for the evaluation of health and disease. It is the purpose of this communication to describe and evaluate a simple quantitative method of examination which also permits careful and repeated study of the exfoliated cells. The method consists of the filtration of a measured amount of urine through a membrane of known surface area and of pore size such that all formed elements in the specimen are retained on the surface of the membrane. The formed elements are fixed and stained on this filter membrane which subsequently is rendered transparent. The cells and casts are examined by means of a light microscope and counted. The results are expressed as the number of formed elements per milliliter of urine. Materials and Method The following are needed: a side arm filter flask, a Pyrex microanalysis filter holder,* gridded

Summary 1. The case histories of three children with recurrent bacterial parotitis are presented. Each patient illustrates a different aspect of the syndrome. One had abscess formation, the second, diffuse suppuration, and the third, a relatively mild but indolent infection which, to date, has been responsible for at least nineteen attacks of parotid swelling. 2. The anatomy and physiology of the normal parotid gland are reviewed. The histologic changes which occur following uncomplicated mumps are described. The manner in which these factors predispose to recurrent bacterial parotitis is discussed. 3. Based on what is known of the normal and infected parotid gland, suggestions are made for the clinical management of these patients.

Serial determinations of rubella hemagglutination inhibition (HI) antibody levels were performed on serum specimens obtained from 223 women who had rubella during pregnancy and their 223 children with congenital rubella. The decline in HI antibody following congenital infection was more rapid than following postnatal infection. By the end of five years, 27 of these children no longer had detectable HI antibody, although all mothers still had antibody. Among 270 children with congenital rubella who had reached their fifth birthday, 50 (18.5%) were seronegative. When 19 such seronegative children were given rubella vaccine [HPV]-77 (high-passage virus strain), only two (10%) of them seroconverted. In contrast, 134 of 135 (99%) normal children of the same age seroconverted.

VIRAL hepatitis and aplastic anemia are not rare. Their concurrence might therefore represent chance. However, within a four-year period, we have encountered 5 patients, all of whom died of aplastic anemia while convalescing from nonepidemic viral hepatitis. This experience suggests that more than chance may be involved and that the sequence of events may be causally related. This communication reports these 5 cases, including 4 autopsies, and compares them with 3 others found in the literature.1 All our patients were children or young adults who lived on Long Island or in New Jersey. Four were males. Pancytopenia followed the onset . . .

W H ~ N virology is surveyed from the vantage point of the beginning of the sixth decade of the twentieth century, the recent great increase in the number of recognized viruses is striking. From 1898 to 1948, 60 viruses were described. By 1959, the number had increased to 200? This recent increase reflects many factors, but perhaps mostly the availability of pure cell line tissue cultures and antibiotics for virus isolation. Many of these viruses are still "in search of diseases." Despite this large number of "available" viruses, the majority of human infections which are labeled clinicMly as "probably viral in origin" are still unidentified etiologically. The surveyor is also impressed by the observation that a single virus might produce multiple clinical syndromes depending upon the age or state of the host. Thus, the rubella virus in the fetus leads to cardiac

A spirillum was repeatedly recovered by blood culture from two children. This organism resembled the Spirillum minus which has long been associated with one form of rat bite fever, Sodoku. In Sodoku the spirillum is usually recovered by animal inoculation and no previous record has been found in which a diagnosis has been made by blood culture. The organisms recovered from the two patients were morphologically indistinguishable from the classical Spirillum minus, but were unique in that they could be maintained for many months on standard liquid and solid bacteriologic media. Their in vivo resistance to penicillin and arsenicals was marked and therefore also unusual. Both patients were seen because of recurrent fever, eruption and symptoms referable to the central nervous system, respiratory and intestinal tracts. The first child was admitted to The Mount Sinai Hospital debilitated and febrile. A spirillum was recovered repeatedly on routine blood culture, although there was no definite history of rat bite. Treatment with arsenicals and penicillin and streptomycin failed and the patient died. The second child was admitted with a history of repeated respiratory infections and indolent skin ulcers and hemiplegia. He had apparently been bitten by a rat while in Florida 3½ years before the spirillum was first recovered from his blood. Treatment with penicillin and sulfarsphenamine was ineffectual. The organism was sensitive in vitro to streptomycin but as much as 2 gm. a day for several months failed to do more than induce several negative blood cultures. Treatment with aureomycin finally succeeded in sterilizing the blood stream and healing the ulcers. Coincident with this there was a striking improvement in the child's general condition. The clinical course of these two patients and the unusual bacteriologic findings set them apart from classical rat bite fever and suggest use of the term "Spirillum Fever."

SummaryA technic for using latex (polystyrene) particles in a serological test with anaerobic diphtheroids is described. Optimum conditions under which latex particles may be used with this bacterial antigen-antibody system are reported. Evidence is presented to indicate a possible immunological relationship between various anaerobic diphtheroids.The authors wish to acknowledge with thanks the capable assistance of Leona Caroline, Helen Lyons, and Dr. Liborio Garcia.

Summary Growth curves of E. coli (0111:B4), L.monocytogenes (4b), and Staphylococcus aureus (Bartlett) were compared at 37° C. in amniotic fluid alone and in amniotic fluid with sterile meconium. Amniotic fluid supported bacterial growth poorly. However, when sufficient meconium was added to the amniotic fluid to give it a yellow-green color (1 per cent), it became a very good culture medium. This was most striking with E. coli and L. monocytogenes and was apparent by 6 hours. These observations suggest that the fetus who remains in meconium-stained amstained amniotic fluid may be exposed to far greater numbers of bacteria than one whose amniotic fluid does not contain meconium.

IT HAS been shown that colonization by one strain of Staphylococcus aureus of the nasal mucosa of adults 1-4 and the nasal mucosa and umbilicus of infants 5-11 interferes with subsequent colonization at those sites by other strains of coagulase positive staphylococcus. This phenomenon, called bacterial interference, has been successfully utilized to curtail epidemics of S aureus in newborn nurseries. A similar protective effect has been demonstrated in adults. In two separate controlled studies, carriers of S aureus who were deliberately colonized following local nasal and systemic antibiotic therapy were protected from recolonization when directly challenged by a second strain of S aureus . 1,2 Cessation of recurrent bouts of furunculosis following recolonization was reported recently in one individual 3 and in one family. 4 The present study demonstrates that artificial colonization with the 502A strain not only protects families against recolonization by the original resident strain of S aureus but