Immunological alterations in anti-HTLV-III negative haemophiliacs and homosexual men in Hungary.

Hungary can be considered as a low risk area for AIDS since no patient with full-blown AIDS or AIDS-related complex has been found in the country. A complex clinical and immunological (T cell subsets, DNCB sensitization test, circulating immune complexes, acid-labile alpha interferon) investigation was performed between November, 1983 and June, 1984 in order to study whether alterations found in symptom-free homosexuals and haemophiliacs in the risk areas for AIDS can be observed in Hungary as well. 38 patients with mild haemophilia, 35 patients with severe haemophilia and 40 homosexual men were investigated in parallel to 37 heterosexual blood donors as controls. Anti-HTLV-III antibodies were measured later in the stored serum aliquots from the same subjects by the indirect membrane immunofluorescence assay. Although specific anti-HTLV-III antibodies were not detected in the haemophiliacs or homosexuals, immunological alterations characteristic for the members of AIDS risk groups in the high risk areas (decrease in the percentage of OKT4 cells and/or decrease of the OKT4/8 ratio) were found in one-third of the homosexuals and haemophiliacs tested. In addition, a significant part of these subjects did not develop delayed type hypersensitivity skin reaction on DNCB rechallenge. These findings indicate that an immunodeficiency independent of HTLV-III infection can be present in two major AIDS risk groups, in homosexual men and haemophiliacs.

Age dependency of the progression of HIV disease in haemophiliacs; predictive value of T cell subset and neopterin measurements.

Sixteen HIV-seropositive haemophiliacs were followed up for 42 months and 9 other patients for 24 months. All patients were infected in 1983 or 1984. T cell subsets and serum neopterin levels were measured twice a year. The patients were divided into three groups according to their age in 1989: group A (children) less than 14 years old (n = 6); group B (adolescents) 14-20 years old (n = 8); group C (adults) greater than 20 years old (n = 11). At the last measurement performed in November, 1989, patients of group A had significantly higher absolute number and percentage of CD4+ lymphocytes and significantly lower serum neopterin levels than patients of group B and C. In addition, the percentage of the activated, CD3+ DR+ lymphocytes was also significantly higher in the adult-adolescent group than in the children group. Until the end of December, 1989, AIDS developed in 0, 1 and 2 patients and ARC was diagnosed in 0, 5, and 2 patients of groups A, B, and C, respectively. The progression of the HIV disease towards AIDS in these patients was predicted by the T cell subset and neopterin measurements performed in 1987. Only those 3 patients who progressed to AIDS had CD4+ cells less than 350/microliters and a neopterin value of more than 20 nmol/l. These findings confirm previous observations indicating that in patients with haemophilia the progression of HIV disease is influenced by age: a relatively slow progression can be expected in prepuberty children.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and mucosal immune responses to rhesus rotavirus vaccine MMU 18006.

Thirty-four children 3 to 20 months of age ingested either 10(5), 10(4) or 10(3) plaque-forming units of rhesus rotavirus vaccine, MMU 18006, which possesses human rotavirus serotype 3 neutralization antigen. Immune responses were evaluated by a plaque reduction neutralization (PRN) assay to rotavirus serotypes 1, 2 and 3 and by a serum IgG, IgM and IgA and fecal IgA class-specific enzyme-linked immunosorbent assay. Homotypic PRN antibody seroconversions to serotype 3 rotavirus were detected in 31 of 34 children (91%), whereas rises in heterotypic PRN antibody to human rotavirus serotypes 1 or 2 were found in only 3 of 21 (14%) (p less than 0.00000001). Thirty of the 34 vaccinated children (88%) had at least one class of rotavirus-specific serum antibody detected by enzyme-linked immunosorbent assay. A rotavirus-specific IgA coproantibody response was seen in 11 of 16 children (69%) following vaccination. Two children who had no evidence of PRN antibody to serotype 3 after vaccination had evidence of both a fecal and a serum rotavirus-specific IgA response, suggesting that in these children the response to the vaccine was primarily mucosal. These data show that orally administered rhesus rotavirus vaccine MMU 18006 elicits local intestinal immunity but produces primarily a homotypic serum neutralization response as measured by plaque reduction neutralization assays.

Three cases of HIV-1 seroreversion.

Three patients were enrolled, two as hemophiliacs, and one with acute EBV infection. Serial serum samples of each patient were tested with at least 3 different HIV antibody EIA tests, an immunofluo-rescent test and two western blots (WB). In the third case, PCR and reverse transcriptase enzyme activity measurement were also done. One of the regularly checked serum samples of hemophiliac patients was reactive with different HIV screening and confirmatory assays. Their next blood samples, two weeks and one month later, respectively, were negative with the same tests. In Case 3. two and a half years after the first examination, the EIA tests results changed to negative, but the WB was still indeterminate. In the case of the two hemophiliac patients, the patients may have been exposed to HIV containing blood products (before 1985), but were not infected. Regular treatment with factor VIII concentrate, in which HIV antigens may be present, can boost the immune response and results in transient seropositivity. In the case of the EBV infected patient, the transient HIV seropositivity may be the consequence of EBV induced proliferation of anti-HIV-antibody producing B cell clones. During our ten year HIV confirmatory practice we tested more than 40000 samples, from which transient seropositivity were observed only in the three cases summarized in this paper.

[Successful electroconvulsive treatment of a schizophrenic patient suffering from severe hemophilia A]. / Súlyos haemophilia A-ban szenvedö schizophreniás beteg szövödménymentes elektroshock kezelése.

Experiences obtained with the electroconvulsive treatment of a schizophrenic patient suffering from severe haemophilia A are reported. No haemorrhagic complications were observed. According to our experiences electroconvulsive therapy can be applied also in severe haemophilia A if satisfactory replacement therapy can be ensured. Similar case has not been found in the literature.

Studies of the sensitivity and reproducibility of commercial kits to detect antibodies to the human immunodeficiency virus.

Nine serial three-fold dilutions (1:1 to 1:6561) were prepared from 18 sera obtained from hemophiliacs confirmed to have antibodies to the human immunodeficiency virus. The dilutions were tested with five different commercial enzyme immunoassay kits and twelve sera were retested 5 to 7 months later by different lots of three kits. The dilution that gave an absorbance (OD) equal to the cut-off OD was considered as the titer of antibody. Sensitivities of the kits were compared by statistical and regression analysis; the same approach was used for studying reproducibility from the results of retesting. The highest titers were found with the Wellcome kit, the lowest with Organon and Pasteur kits, whereas intermediate values were found with the Sorin/Biomedica and Electronucleonics kits. With the Organon and Wellcome kits, excellent reproducibility was observed on later retesting; however, a significant change in titers was seen on retesting the Sorin kit.

Longitudinal immunological follow-up of HIV infected haemophiliacs in Hungary.

Twenty-five haemophiliacs who had been infected with HIV in 1982 or 1983 were followed up from 1986 to 1993. The absolute number of the CD4+ and CD8+ cells, neopterin levels and more recently the percentage of activated, DR+ T lymphocytes were determined twice a year. In most patients a permanent decline in the CD4+ cell count was observed whereas in two HIV-infected haemophiliacs the absolute number of CD4+ cells did not change during the observation period. In these long-term non-progressor patients no clinical symptoms and no increased neopterin levels were observed. T cells subset and neopterin measurements were found to predict the development of AIDS. AIDS developed only in those patients who exhibited both a CD4+ cell count of < 350/microliter and a serum neopterin concentration of > 20 nmol/l. A negative correlation was observed between the percentage of activated. DR+ T lymphocytes and the CD4+ cell counts.

Prevalence of HIV-antibodies in patients with haemophilia in Hungary.

Incidence of HIV antibodies have been studied in 617 patients with congenital bleeding disorders. Screening was performed with the Organon ELISA test, repeatedly positive samples were tested with four different confirmatory assays. HIV antibodies were found in 3/356 patients with haemophilia A, 21/114 patients with haemophilia B, 3/123 patients with von Willebrand disease and in 1/24 patients with other types of congenital coagulation disorders. All the 28 seropositive patients were treated with imported coagulation factor, mostly with factor IX concentrates. No patient treated exclusively with nationally produced factor preparations between 1981 and 1985 was found to be anti-HIV positive.