Of the ever increasing number of viruses known to affect man and higher animals, the virus of lymphocytic choriomeningitis (LCM) was one of the first to be discovered. Indeed, this virus has been known and maintained in the laboratory by passages in a relatively simple host, the mouse, for 35 years. Yet our knowledge of its properties is still scanty when compared with the wealth of information available for other viruses, some of which have come to our attention much more recently. There are at least four reasons which may help to explain this seeming paradox. (1) The early belief that the LCM virus was the frequent cause of human diseases had soon to be abandoned; infections of man with this virus are rare. (2) By way of contrast, laboratory infections are not uncommon and they frequently run severe and even fatal courses. (3) Until recently, the only means of titrating the virus was by mouse inoculation, a method in which accuracy and economy are poorly correlated. (4) The virus is of unusual lability, being quickly inactivated under conditions which leave other viruses intact. Thus, when balancing medical and theoretical importance against personal hazard and technical difficulties, the result was quite unfavorable, and lack of interest was really not surprising.

Lymphocytic Choriomeningitis Virus

Trans-Stadial and Transovarial Development of Disease Agents in Arthropods

During the past 20 years, we have witnessed a tremendous upsurge in research on ticks (Ix odoidea) and tick-borne dis eases in many parts of the world. Results of numerous inv estigations currently under way are thus far only partially reported. Though excellent reviews or "progress reports" of most important tick-borne dis eases have recently been written by highly qualified inv estigators, certain concepts change rapidly. Some aspe cts of the present paper will become out of date during the few months that the manu­ script is in press. No single comp ilation or book listing alI known tick-borne diseases of man has yet been published. Aims here are to (a) provide a briefly anno tated account of human viral infections in which ticks have a sustaining role, to­ gether with important recent references; (b) elucidate principles in epidemio­ logical patterns of this group of disease s; and (c) indi cate needed research areas. Also included, with minimum detail, are references to recent system­ atic, taxonomic, and biological studies undertaken chiefly for clarification of tick-borne epidemiological proble ms. A greater number and variety of tick-borne diseases occur in the Soviet cou ntries than in any other area of the world. The large volume of literature on these illnesses and their vertebrate and inv ertebrate hosts is particularly difficult to review thoroughly, critically, and in detail. We have attempted to note the most important recent studies on each tick-borne disease of humans caused by viruses in this area. Unfortunately, the only book thus far purporting to deal solely with ticks and diseases (7) falls so short of its goal that it cannot conscientiously be recommen ded. In the 1961 volume of the Annual Review of Entomology, Philip & Burgdorfer (217) expertly summarized the general subject of arthro­ pods as reservoirs of disease age nts. Philip's (216) 1963 review of ticks as 1 The survey of the literature pertaining to this review was concluded in April 1965.

Ticks in Relation to Human Diseases Caused by Viruses

Recent investigations on arboviruses and rickettsiae in relation to their vectors have centered upon the isolation of new agents from arthropods and the possible role of arthropods as vectors or reservoirs of microorganisms. There are relatively few papers which analyze in detail the relationships between viruses, rickettsiae, and their vectors. These relationships, character­ ized by benign infections of acarines and vertebrates, were established in the evolutionary development of viruses and rickettsiae, their vectors, host, and the external environment. In the opinion of many authors, as reviewed by Philip (78), these microorganisms were originally symbiotes of acarines and became secondarily pathogenic for vertebrates through the parasitic habits of their arthropod hosts. The presence of intracellular rickettsia-like organisms in ticks supports this hypothesis (103). The transmission of microorganisms by vectors can be classified in differ­ ent ways (62); in this paper, the commonly known classification used by Chamberlain & Sudia (30), distinguishing the biological and mechanical mode of transmission, will be employed. The question of whether arthropods can also be regarded as reservoirs was discussed by Philip (78). In a number of cases, acarines can be considered as reservoirs of viruses and rickettsiae since these microbial agents often persist for several years in their bodies, and may be transmitted through several generations. The majority of these agents, pathogenic for verte­ brates, does not cause any detectable harm to the arthropod vectors; this fact also supports the hypothesis mentioned above. The presence of an infectious agent in a vector depends not only on the arthropod alone, but on all factors determining its ecology (15, 16, 115). In this paper it is intended to make a more or less complete survey of the recent knowledge of the mechanisms of growth and development of viruses and rickettsiae in ticks and hematophagous mites. We shall try to demon­ strate briefly this process from the reception of the infection by the vector to its transmission to the vertehrate host.2

Development of Animal Viruses and Rickettsiae in Ticks and Mites

PURPOSE: This study was initiated to investigate the causes of childhood blindness and visual impairment in the United States. We also sought a particular etiology--congenital lymphocytic choriomeningitis virus (LCMV)--which has been considered exceedingly rare, in a fixed target population of children, the severely mentally retarded. METHODS: We undertook a library-based study of the world literature to shed light on the causes of childhood blindness internationally and to put our data in context. We prospectively examined all consented children (159) at 2 institutions in the United States to determine their ocular status and the etiology of any visual loss present. One of the institutions is a school for the visually impaired (hereafter referred to as Location V), in which most of the students have normal mentation. The other is a home for severely mentally retarded, nonambulatory children (hereafter referred to as Location M). This institution was selected specifically to provide a sample of visual loss associated with severe retardation because the handful of cases of LCMV in the literature have been associated with severe central nervous system insults. Histories were obtained from records on site, and all children received a complete cyclopleged ophthalmic examination at their institution performed by the author. Patients at Location M with chorioretinal scars consistent with intrauterine infection (a possible sign of LCMV) had separate consents for blood drawing. Sera was obtained and sent for standard TORCHS titers, toxoplasmosis titers (Jack S. Remington, MD, Palo Alto, Calif), and ELISA testing for LCMV (Centers for Disease Control and Prevention, Atlanta, Ga). RESULTS: The diagnoses at Location V were varied and included retinopathy of prematurity (19.4%), optic atrophy (19.4%), retinitis pigmentosa (14.5%), optic nerve hypoplasia (12.9%), cataracts (8.1%), foveal hypoplasia (8.1%), persistent hyperplastic primary vitreous (4.8%), and microphthalmos (3.2%). The most common diagnosis at Location M was bilateral optic atrophy, which was found in 65% of the patients examined who had visual loss. Of these, the insults were most often congenital (42.6%), with birth trauma, prematurity, and genetics each responsible for about 15% of the optic atrophy. The second most common diagnosis was cortical visual impairment (24%), followed by chorioretinal scars (5%), which are strongly suggestive of intrauterine infection. Of 95 patients examined at Location M, 4 had chorioretinal scars. Two of these had dramatically elevated titers for LCMV, as did one of their mothers. One of the other 2 children died before serum could be drawn, and the fourth had negative titers for both TORCHS and LCMV. CONCLUSIONS: At both locations studied, visual loss was most often due to congenital insults, whether genetic or simply prenatal. The visual loss at Location V was twice as likely as that at Location M to be caused by a genetic disorder. The genetic disorders at Location V were more often isolated eye diseases, while those among the severely retarded at Location M were more generalized genetic disorders. Our study identified optic atrophy as a common diagnosis among the severely mentally retarded with vision loss, a finding that is supported by previous studies in other countries. In our population of severely retarded children, the target etiology of lymphocytic choriomeningitis virus was responsible for half the visual loss secondary to chorioretinitis from intrauterine infection. This is more common than would be predicted by the few cases previously described in the literature, and strongly suggests that LCMV may be a more common cause of visual loss than previously appreciated. We believe that serology for LCMV should be part of the workup for congenital chorioretinitis, especially if the TORCHS titers are negative, and that perhaps the mnemonic should be revised to "TORCHS + L." Childhood blindness and visual impairment are tragic and co

Childhood blindness and visual loss: an assessment at two institutions including a "new" cause.

ALTHOUGH only 4 years have elapsed since Armstrong and Lillie 1 showed that lymphocytic choriomeningitis is an infectious disease caused by a virus, the evidence indicates that the etiologic agent can be transmitted in several ways. Traub 2 has shown that the virus is discharged in the urine and nasal secretions of infected mice: Findlay and Stern 3 SUCceeded in infecting 3 of 20 mice by nasal instillation of the virus. Finally Wooley, Armstrong, and Onstott 4 have been able to transmit infection occasionally by instilling the virus into the urethra or vagina of monkeys. They have also demonstrated the virus in the seminal fluid and testicular tissue of infected animals. On the basis of these findings, together with the fact that antibodies against the virus were found by them more commonly in adults and especially in criminal and merchant seamen classes, these investi-

https://ajph.aphapublications.org/doi/pdfplus/10.2105/AJPH.29.10.1103

Albert Milzer

Papers

Experimental Infection of Dermacentor Andersoni Stiles with the Virus of Lymphocytic Choriomeningitis.