Harry A. Feldman

Sensitivity of various viruses to chloroform.

Summary A number of myxoviruses were found to be susceptible to chloroform on short exposure in the same way that they are sensitive to the action of ether. On the other hand, the adeno, Coxsackie, echo, polio and Coe viruses tested, were resistant to chloroform.

THE RELATIONSHIP OF TOXOPLASMA ANTIBODY ACTIVATOR TO THE SERUM-PROPERDIN SYSTEM

It was reported in 1948l that a heat-labile serum component, since known as (‘activator”’ was required in order for neutralizing antibodies to affect Toxoplasma gondii. Human serum was found to be the most suitable source of activator because, in the absence of antibody, such serum had no effect upon the parasite. Normal fresh mouse serum also was found not to affect Toxoplasma, but neither would it restore the “activator” effect to serum from which this effect had been removed by heating for 30 minutes at 56’ C. Since mouse serum is poor in C’2 and C’3, the role of complement in the system was explored further. C’1 and C’2l t derived from human complement were restored, both singly and in combination, to inactivated human serum. This restoration resulted in the reconstitution of complement for a hemolytic reaction, but not in the renewal of Toxoplasma activator. This experience led to the conclusion that the hemolytic complement, per se, was not the heat-labile serum component required for the functioning of the Toxoplasma antibody system. It was learned also that proportionately more activator was required for the functioning of the Toxoplasma antibody system than complement was for the hemolysis of sensitized sheep cells. Human sera were found to differ from other animal sera in another respect. Fresh, normal rabbit, guinea pig, rat, monkey, sheep, cow, horse, and dog sera, in the absence of antibody, were found to kill most of the parasites in a suspension and to destroy their afJinity for alkaline methylene blue, which is used as the indicator in the dye test. Specific antibody is presumed not to be present because, when such sera are inactivated prior to examination in the dye test, a negative reaction is generally encountered. Other inactivated animal sera were found to yield significant antibody titers when titrated in the presence of the standard human activator. These reactions are consistent with the patterns observed following experimental infections. Although this nonspecific antitoxoplasmic affect has received scant attention, there has been some feeling that it might play a role in natural resistance. It has been noted that young animals are more likely to succumb to inoculation with parasites than are mature animals. The latter frequently have nonfatal infections despite the fact that parasitemia can be detected. A prominent exception to this is the mature rabbit, which usually dies following the intradermal introduction of virulent parasites. One could assume that this factor reduces the inoculum to the point where the host has an opportunity to provide himself with sufficient protection to withstand the later dissemination of the parasites. I n the case of the intradermal inoculation, the parasites may be

CONGENITAL HUMAN TOXOPLASMOSIS

The congenital form of human toxoplasmosis, the first from which Toxoplasma was isolated, may be the most informative source of knowledge concerning the interrelationship between this parasite and man. It is from this viewpoint, rather than as a pure clinical problem, that the subject will be discussed a t this time. The infectiousness of Toxoplasma for humans was proved when Wolf, Cowen, and Paige’ isolated the parasite from a 31-day-old infant whose illness first had been noted on the third day of life. The presence of chorioretinitis and diffuse encephalomyelitis was corroborated a t autopsy, and Toxoplasma-like organisms were seen in the histological sections. Most importantly, Toxoplasma was demonstrated in mice and rabbits, who succumbed following injection with suspensions of the infant’s brain and spinal cord. Here, then, was evidence, not only that Toxoplasma could produce fatal congenital human disease but, also, that it could give rise to inapparent infections in human adults (for the mother, though well, presumably had been the source of the infection). This was proof, too, that chorioretinitis and encephalomyelitis could result from infection with Toxoplasma. Subsequently, it was demonstrated that microcephaly and macrocephaly, cerebral calcifications, convulsive disorders, and mental retardation could accompany or follow congenital infections, and that such infections were manifested either in utero or a t varying periods following birth. Further progress was slow (and, in some instances, even misleading) until 1948, when new (or improved), precise, and informative techniques, the dye, skin, and complement-fixation tests, became available. These served to stimulate world-wide interest in the parasite and the disabilities that it may produce, so that much new information has been acquired during the past seven years. Because limitations of time and space do not permit a complete discussion of all or much of this newer knowledge, this presentation will be limited to a discussion of the information derived from the preliminary analysis of 187 cases that we have accepted as representing instances of congenital toxoplasmosis. We have nothing to contribute, in a positive sense, to the question of whether congenital toxoplasmosis is ever “inapparent.” Among 176 of these cases, 119 (68 per cent) were 4 years of age or less (60, 1 year or less), 38 (22 per cent) were from 5 to 9 years, and 19 were in the age group of 10 to 19 years. There seemed to be no good reason to exclude these older cases. The dye test antibody patterns of many of the mothers and their offspring are illustrated in FIGURES 1 and 2. As with any serological measurement, there are individual variations, but antibodies tend to persist a t significant levels for many years. No serologically similar group of males has ever been

Removal by Heparin-MnCl2 of Nonspecific Rubella Hemagglutinin Serum Inhibitor

Summary Rubella HI nonspecific inhibitor is removed from serum more effectively by heparin-MnCl2 than by kaolin. Heparin-MnCl2 treatment removes beta-lipoprotein from serum; kaolin does this less efficiently. Among 100 elderly persons, 99 were found to have rubella HI antibodies.

A measles outbreak among adolescents

In a May, 1975, outbreak, 147 adolescents, ages 12 to 19 years, were identified as having measles by a physician or school nurse. One junior high school, with an enrollment of 1,122, contributed 131 of the cases. Of the 147 students, 54 were seen by physicians who also supplied their immunization records; 19 of 54 (35%) had received live measles virus vaccine without measles immune globulin, after age one year. The remaining 35 received: killed virus vaccine only (1), K + L (4), L + MIG (4), L at less than 1 year of age (4), L + ? MIG (4), immune serum globulin only, for exposure (6), no vaccine but history of measles previously (9); history uncertain (3). Hemagglutination-inhibition antibody titers were consistent with the diagnosis of acute measles in 11 children. No index case was identified and no secondary cases occured within the families of the 54 cases. This measles outbreak among seemingly immunized adolescents raises a serious question as to the duration of such protection.

Toxoplasma and Toxoplasmosis

Many mysteries still surround this ubiquitous parasite and the almost universal infection it causes. Usually an innocuous disease, toxoplasmosis in its congenital form can be devastating, causing mental retardation, ocular disease, and death in the newborn. In adults the parasite may be responsible for some forms of eye disease; individuals with impaired immunologic competence are also at serious risk.

Quantitative Biological Assay of Bacterial Endotoxins

Summary The administration of AM-D simultaneously with typhoid endotoxin to mice reduced the 7-day LD50 of the latter approximately 550 to 20,000-fold. This system was used to quantitate the endotoxin contents of minute amounts of purified meningococcal LPS as well as broth culture super nates and cell bodies of these organisms. Small quantities of endotoxin were detected in one meningococcal polysaccharide preparation but not in another which was nonpyrogenic in rabbits.

Meningococcal Group C Subgroup Determinant Detected by Immunofluorescence

Summary The presence or absence of a meningococcal Group C subgroup antigen (C1+) can be detected by immunofluorescence as readily as by a previously reported hemagglutination-inhibition method. When compared in strains isolated from cases and carriers, subgroup negative (C1-) strains seemed to occur more often in cases. The subgroup antigen is widely distributed geographically. The characterization of meningococci by its presence or absence may be of value in epidemiological studies.

Meningococcus and Gonococcus: Never the Twain... Well, Hardly Ever

Among the more intriguing unanswered questions related to infectious diseases are not only how illness and death are induced, but why some of their causative organisms have predilections for certai...

Use of Tissue Culture Cultivated Toxoplasma in the Dye Test and for Storage.

Summary Toxoplasma gondii cultivated in roller tube cultures of Hep-2 cells produce large numbers of free, extracellular parasites for the performance of dye tests. The successful storage of toxoplasma in refrigerated tissue culture preparations for up to 120 days and in the frozen state for as long as 360 days is described.