Defining and measuring exposure in epidemiologic studies of potential zoonoses.

Articles suggesting the zoonotic potential of certain human diseases (eg, multiple sclerosis, rheumatoid arthritis, and leukemia) periodically appear in the literature and frequently receive considerable attention in the popular press. Although various epidemiologic study designs have been utilized to test these hypotheses, defining and accurately measuring animal exposure has been a problem common to most of these studies and in some instances has limited their usefulness. The relative strengths and limitations of the definitions and measurements used most commonly by investigators evaluating potential zoonoses are discussed. In addition, several recommendations for assessing animal exposure in future studies are made.

Donor to host transmission of disease via corneal transplantation.

A literature search was conducted to report all cases of documented transmission of infectious diseases from donors to recipients of corneal transplants. Fourteen such cases have been reported. There is no experimental or clinical evidence to suggest the transmissions of either hepatitis or syphilis via corneal grafting. Available evidence regarding a number of neurologic and other disorders in which a slow virus etiology has been implicated were reviewed. On the basis of this review, we are able to draw certain conclusions and guidelines for selection or rejection of donor material for transplant surgery.

Multiple sclerosis and viruses: an overview.

The evidence for a viral etiology of MS has been reviewed. The strongest evidence favoring a virus is based primarily on epidemiologic considerations. Less convincing evidence comes from pathologic studies, serology, lymphocyte reactivity to viral antigens, and reports of identification of virus in MS tissues. Animal models of viral demyelination exist, which may provide insight into possible etiologic agents and pathogenetic mechanisms. Considering all the data, it is clear that no agent can be convincingly linked to MS at the present time. If a single virus causes the majority of cases of MS, then a morbilliform virus--canine distemper--is a leading contender, because this agent is consistent with the epidemiologic and serologic findings and is highly neurovirulent for animals ranging from mice to primates. Since no virus fulfills the usual criteria for linking an infectious agent to a disease, other possibilities must be considered. If MS is caused by a single virus, it may be a common virus not presently considered as being associated with MS, or an agent as yet unidentified. It is also conceivable that multiple agents, acting alone or in concert, initiate the MS process, perhaps through a common immune-mediated pathway. In this regard, another human demyelinating disease--the Guillain-Barré syndrome--which may in some instances become a chronic remitting and relapsing disorder, is thought to be initiated by multiple infectious agents but to have an immunologic pathogenesis.

Multiple sclerosis-associated agent. Failure of MS brain and serum to depress the polymorph count in normal mice and mice inoculated with cells containing C/type particles.

The groups that originally reported and confirmed the demonstration of a multiple sclerosis associated agent (MSAA) are now, along with others, unable to reproduce this effect. In view of this confusion and the potential importance of this work for multiple sclerosis (MS) we have done a strict double-blind trial using larger groups of mice (10) and counting more cells (900) than in previous reports to offset the high variability of mouse polymorphonuclear neutrophil (PMN) counts. Sera from 5 active MS patients and 4 normal subjects were tested in mice, half of which had previously been injected with PAM line cells (containing C-type particles and subject to reduced cell yield when cultured with MS brain extract). No significant PMN depression was found in either MS or normals on any basis of comparison. However, a significant depression was seen following PAM cell injection irrespective of serum origin. Higher counting accuracy did not reduce PMN variability. A single MS brain specimen was also without effect. consequently we have been unable to confirm the existence of an MSAA as defined by PMN depression in mice.