Biomedical subjects
Publications and source records attributed to M Melbye.
Trichosporon beigelii was isolated from the anal region in 45 (13%) of 343 Danish homosexual men. T. beigelii was also present on the scrotal skin of six anal carriers who were accessible for re-examination, and white piedra of the genital hair was observed in two cases. Because T. beigelii may cause systemic infections in compromised hosts it may pose a threat to homosexuals infected by HTLVIII/LAV virus.
Sera of native inhabitants of Arctic regions were assayed for antibodies to HTLV-I by the ELISA technique followed by competition experiments to confirm antibody specificity. Residents of 7 widely separated Alaskan villages exhibited prevalence rates of 0 to 12% for HTLV-I antibodies. Less than 1% of Greenland Eskimos were HTLV-I antibody-positive. Residents of 3 northern Swedish regions ranged in HTLV-I antibody prevalence from 0 to 5%. Sera of healthy native inhabitants of Alaska and northern Sweden were similarly assayed for antibodies to HTLV-II. No additional sera were shown to be positive for HTLV-II antibodies. While some of the HTLV-I antibody-positive sera exhibited cross-reactivity with HTLV-II antigens, competition experiments using disrupted HTLV-II or purified HTLV-I p24 as test antigens indicated that the primary antibody response in all cases tested was elicited by HTLV-I. Our results show that HTLV-I distribution is not restricted to endemic areas in warm, humid climates, but extends to Arctic regions. Within these regions, HTLV-I exhibits the same restricted distribution seen in other areas where virus infection is prevalent. The Arctic does not seem to be a reservoir for HTLV-II infection. The origin of HTLV-I in Arctic areas is not known. One may speculate that foreign visitors introduced the virus into Aleut and Lapp populations, and that it has been maintained there and restricted in its distribution as a result of close familial relationships.
Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.
A serological survey of 250 outpatients in rural Zaire showed that the prevalence of antibody against HTLV-I, HTLV-II, and HTLV-III, as detected by enzyme-linked immunosorbent assay, correlated strongly with level of antibodies against Plasmodium falciparum. The age curve for the prevalence of antibody against these retroviruses and high titres of antibodies against P falciparum were similar. Tests with control sera obtained from HTLV-III seropositive homosexual men and American subjects repeatedly infected with malaria who had high antibody titres against P falciparum indicated that there was no cross-reactivity between P falciparum and these retroviruses. Immune-complex levels, but not IgG, IgM, or IgE levels, also correlated strongly with seropositivity in the ELISA HTLV-I and HTLV-III assay, although immune-complex-positive control samples were negative. Possible explanations include coincidental distribution paralleling malaria; similar mode of transmission; virus activation and/or enhanced antibody production due to the effect of malaria on the immune system; and false-positive reactivity in the ELISA assay due to cross-reactive antibodies or other unknown factors.
Twenty-seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high-incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty-one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first-degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4+ and OKT8+ cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar to that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement-reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls.
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A human retrovirus--human T cell lymphotropic virus-III (HTLV-III)--has recently emerged as the probable cause of acquired immunodeficiency syndrome (AIDS). In May 1984, 250 outpatients at a hospital in a remote area of eastern Zaire were surveyed for AIDS type illnesses and the prevalence of antibodies against HTLV-III determined by an enzyme linked immunosorbent assay using disrupted whole HTLV-III virus as the antigen. No clinical cases of AIDS were diagnosed among these patients. Overall, 31 (12.4%) had clearly positive ratios (greater than or equal to 5.0) and a further 30 (12.0%) had borderline ratios (3.0- less than 5.0). Western blots of serum samples from subjects with antibodies yielded bands consistent with HTLV-III as found in American patients with AIDS and members of groups at risk of AIDS. The prevalence of antibody was highest in childhood (p = 0.02); among adults prevalence rose slightly with age. HTLV-III antibodies were more common among the uneducated (p = 0.006), agricultural workers (p = 0.03), and rural residents (p = 0.006), but the Western blot bands were generally weak in this group. By contrast, one urban resident had strong bands. The relatively high prevalence of antibodies among the rural poor in this area of Zaire suggests that HTLV-III or a closely related, cross reactive virus may be endemic in the region. A different natural history of infection, perhaps in childhood, may also explain the findings.
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The discovery of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) has opened a window to the understanding of the spectrum of the acquired immunodeficiency syndrome (AIDS) and related clinical syndromes. Analysis of risk factors for seropositivity has shown that HTLV-III is transmitted most efficiently via routes that involve close personal contact or parenteral exposure. Longitudinal studies have shown that HTLV-III infection has a long latent period. The prevalence of AIDS in different geographic areas and among different risk groups appears to depend in part on duration of exposure. Co-factors for AIDS outcome such as manner and route of exposure, underlying immune status, and host susceptibility are also likely to play a role in risk.
77 Scottish haemophiliacs and 22 Danish haemophiliacs were serologically tested for antibodies to human T-cell leukaemia virus III (HTLV-III). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but 2 of the Danish patients had received both locally prepared concentrate and commercial concentrate made from US donor material. 15.6% of Scottish and 59.1% of Danish haemophiliacs were antibody positive (p less than 0.001). None of 11 haemophiliacs not treated in the period 1979-84 was seropositive. 2 (6.7%) of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 23 (39.7%) of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commercially and locally produced factor VIII concentrate, seropositivity was directly correlated with the consumption of commercial concentrate (p less than 0.001) but not locally produced material. These data indicate that European haemophiliacs were exposed to HTLV-III via some factor VIII concentrates obtained from the USA.
In a comparative study of populations at high and low risk of nasopharyngeal carcinoma (NPC), sera from 442 Eskimo and 770 Danish children and adolescents were tested for the presence of antibodies against Epstein-Barr virus (EBV). Eskimo children in Greenland were seropositive at an early age and showed significantly higher titers of IgG antibody to the viral capsid antigen (VCA) (p less than 0.0001) and soluble (S) antigen (p less than 0.005) than Danes matched for age and sex, but had similar levels of IgA antibody to VCA and IgG antibody to the early antigen (EA). The high geometric mean VCA (IgG) titers found in certain age groups of Eskimo children were as high as those previously reported from areas in Africa highly endemic for Burkitt's lymphoma. In Greenland, neither location nor household size was a determining factor for prevalence or titer of VCA (IgG). The high antibody titers among Eskimo children probably reflect exposure to a large inoculum of EBV at the time of primary infection, infection early in life and/or re-exposure due to the higher incidence of EBV infection in Greenland. In view of the high incidence of NPC in Greenland and the known association of this tumor with EBV, we speculate that the time and quantitative aspects of the primary infection are also factors of relevance in the etiology of NPC.
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Sera taken from 250 Danish homosexual men in December 1981 as part of a prospective study of the acquired immunodeficiency syndrome (AIDS) were examined for the presence of HTLV-III antibody with an enzyme-linked immunosorbent assay. Antibody was present in 22 (8.8%) of the men. Seropositivity was most strongly associated with sexual exposure to men in the United States (relative risk 3.5; p less than 0.007). Increased frequency of anal receptive intercourse was also independently associated with seropositivity (p less than 0.05), but age, years of homosexual experience, number of homosexual partners, and use of nitrite inhalant were not independent risk factors. The frequency of seroconversion from absence to presence of HTLV-III antibody appeared to be about 1% a month in this community during December 1981 to February 1983. Of the 22 men who were originally seropositive, two (9%) subsequently developed AIDS as defined by the Centre for Disease Control and two (9%) others the AIDS related complex. Blood was taken in addition from two of the men to develop AIDS earliest in Denmark (diagnosed 1981) at the same time as the initial survey in 1981; both were seropositive. The spread of HTLV-III from high to low risk areas and the subsequent appearance of illnesses related to AIDS in the seropositive group support the hypothesis that HTLV-III is causally related to the development of AIDS.
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To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.
Interviewed to obtain the first quantitative data from Scandinavia on lifestyle factors of possible importance for their health were 259 Danish male homosexuals. The frequency of various sex acts, frequency of change in partner, visits to the United States, sexual contacts with victims of the immune suppression syndrome, education, smoking and drug habits, and recent medical problems were recorded. Of those interviewed, 170 were from the Danish capital, Copenhagen, and 89 were from a smaller provincial town, Aarhus. Sexual habits and most other factors were very similar in men from the two cities. Furthermore, the sex habits of those who had visited a venereal disease clinic were similar to those of the group as a whole except for a frequent change of partners. Our data on level of sexual activity resemble those available for the San Francisco Bay area of 1970. The Copenhagen men, however, had more partners per year, had more sexual contact with U.S. citizens and immune suppression syndrome victims, and more had used nitrite inhalation than the men in Aarhus. The frequency of venereal disease was the same in the two groups, but the Danish cases of Kaposi's sarcoma and the acquired immune deficiency syndrome all have come from the Copenhagen area. Two of those interviewed have developed AIDS subsequent to homosexual contact with a case of Kaposi's sarcoma.