Hans Kerzel Andersen

Clinically evident, non-terminal infections with herpesviruses and the wart virus in immunosuppressed renal allograft recipients.

The clinical incidence of herpes simplex lesions, herpes zoster, cytomegalovirus infection, and warts has been determined in a group of renal allograft recipients. Herpes simplex lesions appeared to be no more common after transplantation than before in those patients subject to recurrent attacks. Among 74 patients there were seven cases of herpes zoster and seven serologically proved cases of cytomegalovirus infection with clinical manifestations. The incidence of warts increased with length of time after transplantation, 42% of patients being affected more than one year after transplantation. All of the viral infections studied behaved as in healthy adults, and serious illness, dissemination, wide-spread lesions, and complications were not seen. No factors other than immunosuppression and steroid therapy could be identified with certainty as predisposing to these infections.

Is Multiple Sclerosis Caused by a Dual Infection with Retrovirus and Epstein-Barr Virus?

Although the etiology of multiple sclerosis is as yet unknown, epidemiological observations strongly point toward one or more infectious agent(s) being involved in the disease. In recent years some studies have indicated involvement of retrovirus in multiple sclerosis (MS). However, an intrafamilial epidemiological study revealed that MS and the known human retroviruses had a divergent epidemiology. Some studies have shown the association of Epstein-Barr virus (EBV) with MS and one recent study revealed dual infection by retrovirus and EBV in a cell line established from a patient with an MS-like disease. Our hypothesis for the development of MS and MS-like diseases is that a hitherto uncharacterized retrovirus is the etiological agent, but development of neurologic disease is related to or even dependent on a delayed EBV infection. The dual infection hypothesis is analyzed and found to be consistent with the epidemiological characteristics of MS.

Seminal fluid excretion of cytomegalovirus related to immunosuppression in homosexual men.

Seminal fluid samples from 84 Danish homosexual men were successfully cultured to determine the prevalence of cytomegalovirus excretion. Ten (15%) out of 66 men positive for the antibody were found to be excreting the virus. Although the proportion excreting was inversely related to age (p less than 0.01), three men aged over 30 and with many years of homosexual experience excreted the virus. In addition, a 50 year old man with Kaposis sarcoma excreted the virus. A further study of the ratio of T cell helpers to suppressors in the men aged over 30 and a series of age matched non-excreting homosexual control or heterosexual men showed that those excreting cytomegalovirus in their seminal fluid had statistically lower ratios (all less than 0.77) than the controls (p less than 0.05). Excretion of cytomegalovirus may be related to re-emergence of latent infection in immunosuppressed homosexual men.

In vitro stimulation of human lymphocytes by purified cytomegalovirus.

Lymphocytes from 19 healthy donors were tested against purified cytomegalovirus (CMV) strain Ad 169, in a lymphocyte-transformation test. The test was performed in microcultures using various preparations and concentrations of antigen. These included, besides purified CMV, CMV-infected cells, herpes simplex virus type 1 antigen, and control antigens. Lymphocytes from CMV-seropositive donors were stimulated by purified virus and infected cells, whereas lymphocytes from seronegative donors did not respond. Similarly, only lymphocytes from herpes-seropositive donors did respond to herpes antigen. With these preparations of antigen the test was found to be sensitive and specific.

Humoral and Cellular Responses to Pneumocystis carinii, CMV, and Herpes simplex in Patients with AIDS and in Controls

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Increased risk of multiple sclerosis after late Epstein-Barr virus infection*: A historical prospective study†

The objective of this study was to evaluate the association between infectious mononucleosis (IM) and multiple sclerosis (MS). In a historical prospective study we used records from the Danish State Serum Institute in which heterophile antibody tests (HA) for infectious mononucleosis were performed for all Danish patients for a number of years. Included in the analysis were 6853 HA‐positive people and 12,886 HA‐negative people. A search for the presence of these people in the nationwide Danish Multiple Sclerosis Registry (DMSR) was performed. Among the HA‐positive people 16 cases of MS were found. The expected number for a matched Danish population was 5.70, the risk ratio being 2.81. No cases had developed MS before contracting infectious mononucleosis. Among the HA‐negative people the expected number of MS patients were found. Although Epstein‐Barr virus is not suggested in itself to be the cause of multiple sclerosis, a hypothesis is put forward that it is a cofactor in the pathogenesis of this disease.

Stimulation of human lymphocytes by cytomegalovirions and dense bodies

Lymphocytes from healthy adult individuals were examined for their ability to incorporate thymidine in the presence of cytomegalovirus (CMV) and dense bodies. It was found that lymphocytes from donors with antibodies to CMV were stimulated to incorporate thymidine-14C both by preparation of CMV and CMV dense bodies. Lymphocytes from CMV seronegative donors did not respond. Dilution experiments and the dose-response curve indicate that the stimulation induced by the dense body preparation was not caused by the small amounts of contaminating CMV particles. These results indicate that in healthy human adults there is a correlation between CMV seropositivity and in vitro lymphocyte transformation, induced by either CMV or by dense bodies.

A Prospective Study on Infection with Cytomegalovirus in Renal Allograft Recipients Immunosuppressed with Cyclosporine a and Low Dose Prednisone

To investigate the course of infection with cytomegalovirus (CMV) in renal allograft recipients treated with cyclosporine A, 10 patients were followed for 1 year after transplantation. Virus cultures from blood, urine and throat washings were performed employing a quantitative technique. Complement-fixing and IgM antibodies to CMV were measured at scheduled intervals. The incidence 90% and course of CMV infections were found not to differ from those reported in patients receiving conventional immunosuppressive therapy. The quantitative virus cultures showed a consistent pattern with viremia most prominent at the beginning of an infection, and the highest concentration found in the one patient who developed symptoms of viral disease. It is suggested that information about the concentration of virus in a specimen will improve the diagnostic value of virus cultures in this group of patients.

Cytomegalovirus antibodies in epileptics receiving diphenylhydantoin

Cytomegalovirus (CMV) antibodies were determined by indirect haemagglutination in 53 epileptics receiving long‐term diphenylhydantoin (DPH) therapy and in 53 matched controls. Absorption of serum IgG, IgA and IgM performed in 12 sera showed that the antibodies were of the IgG class. A decreased incidence of high CMV antibody titres ( 320) was found in epileptics (11.3%) compared with controls (34.0%) (0.02 > P > 0.01), whereas antibody titres 40 were found in 37.7% of epileptics and in 45.3% of controls (n.s.). The CMV antibody incidence and titre range were similar in patients with symptomatic (37.9%) and idiopathic (37.5%) epilepsy, suggesting that the DPH treatment was responsible for the decreased antibody occurrence in patients. No correlation between CMV antibody titres and the serum immunoglobulin levels or the DPH concentration or clearance could be established in the epileptics.