Biomedical subjects
Publications and source records attributed to H K Andersen.
A case of endocarditis with vegetations on the tricuspid valve caused by Capnocytophaga canimorsus is described. Extensive diagnostic investigations preceded the diagnosis, including blood cultures, 34 of which were sterile. A possible role of the pulmonary circulation in the negative blood cultures is discussed.
A patient sustained a knife wound while cleaning eels and subsequently severe wound infection developed. Vibrio vulnificus was isolated from the wound and, on the basis of this, the main features of the epidemiology of the bacteria and the typical clinical pictures are reviewed.
Puumala virus belongs to the hantavirus group and as other members of the group it can cause acute renal insufficiency. Other hantaviruses are responsible for Korean hemorrhagic fever and other hemorrhagic fevers with renal involvement. In Scandinavia, hantavirus nephropathy is better known as nephropathia epidemica. Hantavirus cause asymptomatic infections in mice and rats and the virus is thought to be transmitted to man via inhalation of desicated saliva, urine or feces from infected animals. In the other Nordic countries, the bank vole (Clethrionomys glareolus) is the commonest natural host. Laboratory infections from rats have been reported from all over the world. The disease presents with fever, back and/or abdominal pain, acute renal insufficiency and a bleeding tendency. The latter is usual less pronounced in the European than in the Asian forms of hantavirus infection. The disease is commoner in men and is endemic in forested areas. The greatest incidence is seen in those years when the numbers of mice are greatest. The mortality in nephropathia epidemica appears to be less than 0.5% in contrast to a mortality of about 10% in Korean hemorrhagic fever. Diagnosis is made by demonstration of a significant increase in antibody titer to hantavirus. Treatment is symptomatic and consists primarily of restitution of fluid and electrolyte balance, at times with dialysis. After recovery from hantavirus infection renal function returns to normal. The incidence and prevalence of nephropathia epidemica in Denmark are unknown. The first two cases of Puumala virus infection in Denmark are reported.
An antibody capture enzyme-linked immunosorbent assay (ELISA) was developed for the detection of immunoglobulin D (IgD) antibodies to cytomegalovirus (CMV) in sera from blood donors and various groups of patients infected with CMV. This method has previously been found especially valuable in detecting specific antibodies of the IgM, IgE, IgA and IgG class in patients with CMV infection. Specific CMV IgD antibodies were found in 37% of CMV seropositive blood donors and in 47 (88%) of the 53 patients investigated, including bone marrow transplant and renal allograft transplant patients, patients with CMV mononucleosis, neonates with CMV infection and AIDS patients with CMV infection. The highest IgD reactivity was found in patients having either a primary post-transplant CMV infection or CMV mononucleosis. The IgD reactivity in patients with AIDS and in neonates was low. It was also found that in the acute phase of CMV infection the development of CMV antibodies of the IgD class was similar to the development of antibodies of the other classes. The maintenance of IgD activity in some patients together with the presence of CMV IgD antibodies in a great proportion of the blood donors indicates that the development of CMV IgD antibodies resembles that of the IgG class. Determination of specific IgD antibodies offered no advantage over determination of specific antibodies of the IgM, IgE and IgA classes in the diagnosis of CMV infection.
Antibody-capture enzyme-linked immunosorbent assay (ELISA) using enzyme-labeled cytomegalovirus (CMV) nuclear antigen is a reliable and easily performed test suitable for routine use. As the serologic response to CMV infection may, however, vary considerably among patients, we have studied the kinetics of CMV-specific immunoglobulin M (IgM), IgE, IgA, and IgG antibodies in 352 sera from 61 patients by using antibody-capture ELISA and complement fixation (CF) tests. In a CMV mononucleosis group (n = 17), most patients had antibodies of all four immunoglobulin classes, but antibody levels decreased rapidly, with half the patients having a borderline-positive or a negative reaction for all classes, except IgG, 2 months after the appearance of symptoms. Twelve patients with a primary CMV infection after renal or bone marrow transplantation also developed all immunoglobulin-class antibodies. In only two patients did CMV IgM and IgE antibodies precede seroconversion of CF antibodies, and in one patient, these antibodies lagged months behind. Most patients had all classes of CMV antibodies, except IgA, for a year or more. Among 10 transplant patients with a secondary CMV infection, 50% had long-lasting IgM antibodies, and very few had IgE or IgA antibodies, but all had IgG antibodies to CMV. In 13 infected infants, the CMV-specific serologic response was also characterized by long-lasting IgM, IgE, and IgG antibodies. Two patients did not develop detectable IgM antibodies, and one of these did not show IgE antibodies either. The IgA response in infants as a whole was lacking; a few, however, were borderline positive. Of the nine acquired immunodeficiency syndrome patients with CMV infection studied during their last year of life, only one had antibodies in all four classes, the rest had only CF antibodies, and all except for one had IgG-class antibodies. All sera studied were also tested against a control antigen produced from noninfected cell nuclei. It was found that some patients developed antibodies to nuclear antigens in parallel with the rise in specific antibodies. The nonspecific antibodies occurred in all four classes, but most often they were of the IgM class. Addition of unlabeled control antigen to the conjugates was not always sufficient to abort this nonspecific reaction.
This study describes the results of testing 92 serum samples, including 10 umbilical cord serum samples, from 38 cytomegalovirus (CMV)-infected neonates for CMV-specific immunoglobulins E (IgE) and M by antibody-capture enzyme-linked immunosorbent assays with enzyme-labeled CMV antigen. All infants excreted CMV in the urine. It was demonstrated that the CMV IgE test was more sensitive than the CMV IgM test in diagnosing CMV infection in neonates by serology. Thus, the sensitivity for the IgE test was 82%, whereas for the IgM test it was only 66%. Furthermore, the CMV-specific IgE response, expressed as absorbance, was higher than the specific IgM response in 91% of the 76 sera which contained antibodies of either one or both immunoglobulin classes. Forty-six control sera, including 18 umbilical cord sera, from 46 neonates from whom CMV was not isolated were also tested. Most sera were negative. Three infants, however, had CMV antibodies of one or both classes, indicating infection. The level of total serum IgE was controlled in 24 of the sera from the CMV-infected neonates, but in none of the cases was the level elevated. No correlation was found between the reactivity of the antibodies in the two immunoglobulin classes and the level of CMV in urine.
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.
Chronic graft-versus-host disease (GvHD) in bone marrow allograft recipients is frequently preceded by a cytomegalovirus (CMV) infection. To elucidate whether an immune reaction of transplanted donor cells against CMV was involved in the pathogenesis of chronic GvHD, the effect of donor pretransplant CMV immune status on chronic GvHD incidence was analyzed. In 43 bone marrow recipients at risk, the 2-yr cumulative chronic GvHD probability was 55% when the donor was immune, in contrast to 16.5% when the donor was non-immune (p less than 0.002). No correlation between recipient pretransplant CMV immunity and chronic GvHD was observed. Donor CMV immunity did not correlate with acute GvHD or posttranplant CMV infection and seemed to predispose for chronic GvHD regardless of donor and recipient age. However, the proportion of CMV immune donors increased with increasing donor and recipient age. This may account for the higher incidence of chronic GvHD in older patients. The present study suggests that chronic GvHD may be mediated by a reaction of immune donor cells against CMV infected recipient cells.
An antibody capture enzyme-linked immunosorbent assay (ELISA) that uses horseradish-peroxidase-labeled antigen for the detection of immunoglobulin G (IgG) antibodies to cytomegalovirus (CMV) is described. A microtiter plate was coated with anti-human IgG and consecutively incubated with serum specimens, enzyme-labeled CMV antigen made from CMV-infected cell nuclei, and substrate. The CMV IgG antibody content was determined spectrophotometrically and expressed as absorbance. Furthermore, to reveal any nonspecific reactions, all sera were tested against an enzyme-labeled control antigen made from uninfected cell nuclei. The problem with nonspecific reactions was small and was circumvented by the addition of unlabeled control antigen to the conjugates. For epidemiological studies the test was not as sensitive as other serological tests. On the other hand, the IgG antibody capture ELISA was highly sensitive for detecting the serological antibody response in patients with primary and recurrent CMV infections. Thus, one positive serum remained positive at a serum dilution of 1:10(7). The specificity of the test was shown by a blocking experiment and by testing 126 complement fixation-positive sera, of which 97% were positive. There was a rather good correlation between the complement fixation test and the IgG antibody capture ELISA (rs = 0.79, P less than 0.001). The test is especially useful when tests for CMV antibodies of the IgM, IgA, and IgE classes are run by similar antibody capture ELISAs, since the same procedure and conjugate are used.
Five fatal cases of CMV associated interstitial pneumonia occurred among 20 patients who had received allogenic bone marrow transplantation for acute leukemia or aplastic anaemia. This outcome was analysed in relation to prospectively obtained data on complement fixing (CF) and IgM anti-CMV titres and excretion of CMV in urine or pharynx. Altogether 16 patients had primary or reactivated CMV infection. Five of these patients receiving corticosteroids at the time of infection, at a dose of more than 1 mg/kg/day, failed to mount a significant CF antibody response, excreted large amounts of virus, and died from pneumonia, while the remaining 11 infected patients obtained high CF antibody titres and showed no severe symptoms related to CMV infection. IgM antibodies occurred simultaneously with CF antibodies in most cases of primary and reactivated infection. The results of the study suggest a protective role of the humoral immune response to CMV infection in BMT recipients, and passive immunisation with CMV hyperimmune globulin should be attempted especially in patients given additional immunosuppression with high dose corticosteroids.
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 Kaposi's 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.
Two-hundred and fifty-nine male homosexuals (HS) of a large and a small Danish town were studied for antibodies to various virus and their statistical relationship to sex habits, drug use and other lifestyle factors. Prevalence rates against cytomegalovirus (CMV) were 86.7% of HS men from Copenhagen and 73.3% of HS men from the smaller community of Aarhus, against 30% of a control group. Antibody prevalence in homosexuals was significantly related to number of years of homosexual activity (p less than 0.0001), number of partners (p less than 0.01), nitrite inhalant use in the past year (p less than 0.01), and independently to venereal disease during the past year (p less than 0.01). Titer levels correlated with number of years of HS activity (p less than 0.001), number of partners (p less than 0.01), and independently with nitrite use in the past year (p less than 0.01). The association between lifestyle and antibodies was not detectable for VCA-IgG, VCA-IgA, VCA-IgM, and EA antibodies to Epstein-Barr virus (EBV) or for antibodies to herpes simplex virus type 1 and type 2, parvovirus and rotavirus. In a subset of 78 HS men, T-helper/T-suppressor ratio was determined. No correlation was found between level of ratio and either prevalence or titer of antibodies against CMV, EBV-components or herpes type 1 and 2.
Danish children brought to Greenland have somewhat higher mean titers of antibodies to Epstein-Barr virus than do Danish children in Denmark, although their titers are lower than those found in Eskimo children. This study presents the first evidence of increases in Epstein-Barr virus titers in migrant children.
Samples of milk from 23 mothers attending the department of obstetrics and gynaecology and 36 who donated milk to the department's milk bank were cultured for cytomegalovirus. Virus was isolated from samples from 12 of the milk donors but none of the mothers attending the department; follow-up studies during lactation in seven of these 12 women showed that five continued to excrete the virus. Samples were taken on three occasions from one woman who regularly excreted high titres of the virus. Storage at -20 degrees C for over three days reduced the titre by over 99%; after pasteurisation at 63 degrees C for eight minutes the milk did not contain any viable virus. It is recommended that raw banked milk used for feeding preterm babies should be kept frozen for at least 72 hours before feeding.
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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 (greater than or equal to 320) was found in epileptics (11.3%) compared with controls (34.0%) (0.02 greater than P greater than 0.01), whereas antibody titres greater than or equal to 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.
Antibodies to whole pigeon serum (PS) and pigeon dropping extract (PDE) were investigated in pigeon breeders and controls by an enzyme-linked immunosorbent assay (ELISA). The optimal antigen concentration was in the range of 3-30 microgram protein/ml for both PS and PDE. PDE antibody titres greater than or equal to 10240 were found in three (75%) of four patients with pigeon breeders' disease (PBD) and in 19 (13.6%) of 140 other pigeon breeders (P = 0.011). PS antibody titres greater than or equal to 10240 occurred in all four (100%) PBD patients and in only seven (5.0%) of 140 other breeders (P = 0.0002). In 85 blood donors antibodies in low titres against PS and PDE occurred in 4.7% and 7.1%, respectively. By immunodiffusion three or more precipitin lines were found more often in PBD patients than in other breeders (P = 0.0006), and the highest ELISA antibody titres occurred in patients with precipitating antibodies. No correlation between P blood group phenotypes or anti-P1 antibodies and respiratory symptoms or antibodies to pigeon antigens could be demonstrated.
Young BALB/c mice inoculated intraperitoneally with herpes simplex virus type 2 develop focal necrotizing hepatitis. After infection, the livers of these mice show increasing virus titers, which reach a maximum on day 3 after infection; this is followed by a dramatic decrease in the amount of virus recovered on days 4 and 5. This decrease in virus content is accompanied by a progressive infiltration of the lesions with mononuclear leukocytes and an apparent resolution of the lesions. Adoptive transfer of immune spleen cells from mice infected 6 days earlier accelerated this process. When 50 x 10(6) to 100 x 10(6) immune spleen cells were transferred 24 h after infection, the inflammatory response and the clearance of virus from the livers were advanced by almost 2 days. As few as 12 x 10(6) immune spleen cells accelerated the healing process, whereas fewer immune cells, disrupted immune cells, or normal spleen cells did not have an effect. The protection conferred by herpes simplex virus type 2-sensitized immune spleen cells was specific since mouse cytomegalovirus- or vaccinia virus-sensitized immune spleen cells had no effect on the course of infection with herpes simplex virus type 2, whereas some cross-reactivity was observed between herpes simplex virus types 1 and 2. This model seems to be suitable for examining the immunological mechanisms that are active during recovery from visceral herpes simplex virus infections.