The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex.

OBJECTIVE: To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS). DESIGN: Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING: Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS: One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES: Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS: Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION: Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.

Clinical significance of cytomegalovirus viremia in bone marrow transplantation.

Cytomegalovirus (CMV) viremia was systematically studied in 56 patients having undergone bone marrow transplantation for leukemia or aplastic anemia. Of the patients who survived at least three months, 57% had CMV viremia with a frequency peak between the 7th and the 9th weeks. We describe possible clinical signs associated with viremia, particularly late peripheral and/or central thrombocytopenia. The occurrence of viremia was studied according to the specific preexisting immune status of recipients and donors; granulocyte transfusions and graft-versus-host disease. The relationship between these parameters and viremia provides a basis for the analysis of prophylactic treatments of CMV infection.

Legionnaires' disease after bone marrow transplantation.

Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared.

Transient hydrops fetalis associated with intrauterine cytomegalovirus infection: prenatal diagnosis.

BACKGROUND: Intrauterine cytomegalovirus infection is usually unrecognized during pregnancy. However, in some cases, ultrasound abnormalities can be observed in association with cytomegalovirus infection. CASE: The prenatal diagnosis of cytomegalovirus infection in a fetus with transient hydrops is reported. Fetal ascites was first recognized by routine ultrasound examination at 20 weeks' gestation. Hydrops fetalis was obvious at 23 weeks and completely resolved 1 week later. Cytomegalovirus was detected from amniotic fluid samples by centrifugal culture and direct immunofluorescent examination. The diagnosis of maternal primary infection could be established retrospectively by demonstrating immunoglobulin (Ig) G and IgM seroconversion on sequential sera. The pregnancy was electively terminated. Autopsy findings were consistent with fetal disseminated infection. CONCLUSION: Transient hydrops fetalis in association with intrauterine cytomegalovirus infection is infrequent. The resolution of hydrops fetalis could be explained by hepatic dysfunction of limited duration. Amniotic fluid culture is a reliable approach for diagnosing intrauterine cytomegalovirus infection, but does not predict the severity of the disease or the outcome of the pregnancy. The long-term clinical significance of intrauterine cytomegalovirus infection has to be established.

The use of labeled fusion protein for detection of B19 parvovirus IgM antibodies by an immunocapture test.

A new anti-B19 IgM ELISA was developed taking advantage of antibody-capture with biotinylated fusion protein as antigen. Specificity was examined using serum IgM antibody positive for rubella, hepatitis B core antigen, cytomegalovirus and Epstein-Barr virus as well as with sera positive for rheumatoid factors or antinuclear antibodies. The specificity was found to be 96%. Of one hundred serum samples compared using the new ELISA or the standard MACRIA tests for the presence of B19 IgM, 88 gave the same results. Fifty-three were negative and 35 were positive. Six sera were ELISA-negative MACRIA-positive, and six MACRIA-negative ELISA-positive. Thus, the ELISA gave 90% agreement with MACRIA. In a clinical study with 725 sera from suspected B19 infections, 161 (22%) were found positive by ELISA. The positive sera were from patients suffering from arthritis (35%), rash (35%), acute or chronic erythroblastopenia (21%), pancytopenia (5%), vascular purpura (2%) and lymphadenopathy (2%). A series of serum specimens obtained from two-B19 infected individuals were also studied. The IgM antibody became undetectable after four months.

Comparison of MRC-5 and continuous cell lines for detection of cytomegalovirus in centrifugation cultures.

Continuous cell lines were assessed for use for rapid human cytomegalovirus (HCMV) detection procedures combining tissue culture, centrifugation, and immediate early antigen (IEA) immunostaining. Human cells (MRC-5 embryonic fibroblasts, U-373MG astrocytoma cells, differentiated teratocarcinoma (Tera-2) cells), murine cells (BALB/c-3T3 and Y-1 cells), BHK21 hamster cells, and mink lung (ML) cells were first inoculated with HCMV laboratory strain. IEA synthesizing cells were detected by immunoperoxidase assay using a monoclonal antibody. ML cells and differentiated Tera-2 cells exhibited more positive cells than MRC-5 cells. BHK21, and MRC-5 cells were equivalent in sensitivity whereas U-373MG, BALB/c-3T3, and Y-1 cells had only reduced IEA positive cells. When 63 urine specimens were inoculated onto MRC-5, ML and differentiated Tera-2 cells, 20 (31.7%) were positive in MRC-5 cells versus 18 (28.5%) in ML or Tera-2 cells. Moreover, greater numbers of infected cells were detected in MRC-5 cells than in these two cell lines. MRC-5 cells were superior for detection of HCMV in clinical samples by centrifugation cultures.

Measurement of bacterial and fungal air counts in two bone marrow transplant units.

We evaluated air contamination with bacteria and fungi in a transplantation unit, successively housed in two buildings. Bacterial air contamination was least in laminar air flow rooms, and reduced in ultraclean air rooms in comparison with conventional rooms. Similar results were obtained with culture of air for fungi.

[Bacteriological, parasitological and virological study of the digestive flora in alpha-chain disease]. / Etude bactériologique, parasitologique et virologique de la flore digestive dans la maladie des chaînes alpha.

Intestinal flora was explored in twelve patients affected with alpha-chain disease at different stages (stage A: 2 cases; stage B: 6 cases; stage C: 4 cases). Bacterial overgrowth in the jejunum was observed in 11 cases, but intestinal flora was diverse and no one species was always present; although a 3-month oral antibiotic treatment induced complete remission in one patient (stage A) it was not possible to demonstrate any pathogenic bacterial species. Intestinal lambliasis was present in 40 p. 100 of cases. Virologic studies were negative. At stages A and B of the disease, antibiotic treatment was able to improve malabsorption and/or plasma protein digestive losses in 62 p. 100 of cases; this effect seemed related to the reduction of the bacterial flora and to giardiasis eradication.

[Fatal herpetic hepatitis in an apparently healthy adult]. / Hépatite herpétique mortelle chez un adulte apparemment sain.

The authors report the case of a 46-year old patient who died from fulminant herpetic hepatitis. No cause of immuno-depression was documented in this patient. No skin or mucosal herpetic lesion was found except a questionable urethritis. Herpes virus was demonstrated in the hepatocytes by electron microscopy and isolated from the serum. It was identified as herpes virus hominis type II. The low titer of circulating antibodies did not permit the distinction between herpetic primo-infection and reactivation. The features of the hepatic injury are discussed and compared with previous reports. An active diagnostic approach of herpetic hepatitis is considered.

[4 new cases of neuromyositis, one of them associated with HTLV-I infection]. / Quatre nouvelles observations de neuromyosites, dont un cas associé à une infection par HTLV-I.

Neuromyositis is a very rare type of polymyositis where, beside the usual muscular manifestations, there are signs of peripheral neuropathy which can be found at clinical, electromyographic and/or pathological examination. We have seen between 1983 and 1990 four cases of neuromyositis. The neurological disorder was an axonopathy in two cases which is usual in neuromyositis; in the other two cases, there was a polyradiculoneuritis which seems to be very rare in this syndrome. In the four patients the disease was particularly severe and unresponsive to treatment. One of our patients had HTLV-I infection diagnosed by polymerase chain reaction amplification and in situ hybridization, while the serological test was negative. To our knowledge only three cases of HTLV-I associated neuromyositis have been reported in the literature.

[Capnocytophaga infections. Apropos of 8 cases]. / Infections à Capnocytophaga. A propos de huit observations.

Eight Capnocytophaga infections are described: bacteremia in immunodepressed patients (three cases), endocarditis (one case), pneumopathy (one case), buccal infection (two cases) and endometritis during use of an intrauterine contraceptive device (one case). The role of this bacterium in infections presented by immunodepressed patients is discussed in terms of literature data. Identification of the genus posed no problems. Species diagnosis is considered in terms of the use of conventional biochemical tests and the API ZYM collection.

[Chlamydia trachomatis: risk factors in women in the Parisian region. Importance of smoking and cervical ectropion]. / Chlamydia trachomatis: facteurs de risque chez les femmes de la région parisienne. Importance du tabagisme et de l'ectropion cervical.

A study of chlamydial infection and its clinical correlates was undertaken collaboratively among french women attending sexually transmitted disease (STD, prenatal, and teen clinics (n = 148). A complete sexual and gynecologic history and pelvic exam was performed on all women. Endocervical and urethral cultures were obtained for C. trachomatis and N. gonorrhoeae. Reason for visit included suspected STD in 97% of STD, 5% of prenatal and 17% of teen women. N. gonorrhoeae was isolated from STD clinic patients only (17%). C. trachomatis was found in 22% of teen, 17% of STD and 2% of prenatal clinic women. C. trachomatis was significantly associated with smoking, a history of urethral discharge in the male partner, and endocervical ectopy > 50% of total cervical surface.

[A microbiological study of swabs taken laparoscopically in cases of salpingitis and tubal sterility. Research for Chlamydia trachomatis and for mycoplasmas (author's transl)]. / Etude microbiologique des prélèvements coelioscopiques dans les annexites et les stérilités tubaires. Recherche de Chlamydia trachomatis et de mycoplasmes.

Research was made for chlamydia trachomatis and ureaplasma urealyticum in the peritoneum and the tubes of 99 women divided into 4 groups: 17 of them were being investigated because of acute salpingitis (Group A), 17 were being investigated for tubal sterility with chronic inflammation diagnosed laparoscopically (Group B), 29 were being investigated for tubal sterility without any laparoscopic evidence of inflammation (Group C) and 36 women had absolutely normal pelves and were being investigated for sterility. These were the control group (D). Swabs were also taken from the lower genital tracts as well as serological tests for chlamydia trachomatis and cytological samplings of the fluid from the Pouch of Douglas and the histology of the tubes. In the 17 women who had acute salpingitis the swabs 4 cases of C.T. and 4 of U.U. In the 46 women who had tubal sterility the laparoscopic swabs showed cases of C.T. and 7 of U.U. The swabs were most often positive in Group B. This group is characterised by a special appearence of the inflammation, with fluid present and viscous adhesions as well as peritoneal inflammatory cysts. These altogether help to make a presumptive diagnosis of C.T. infection on laparoscopy. In the control group of 36 cases there was no sign of C.T. in any case, although 2 swabs from the peritoneum showed U.U. So there is a statistically significant difference between the groups that were suspicious and the control group whether the results were obtained by cultures or by serological diagnosis. On the other hand there is no definitive difference as far as U.U. is concerned. These observations, which are similar to those published by other authors, lead us to think that micro-organisms and especially chlamydia trachomatis could be the bacteriological agent responsible for chronic inflammatory states found so frequently in women with tubal sterility.

[Diagnostic value of the study of anti-Chlamidia antibodies in salpingitis. 379 cases]. / Intérêt diagnostique de la recherche des anticorps anti-chlamydiens au cours des salpingites. 379 observations.

Antibodies to Chlamydia were assayed by complement fixation (CF) and inclusion indirect immunofluorescence (IFI) in sera collected from 379 patients with salpingitis: 30.3% of the patients had total and IgM antibodies at IFI and CF antibodies (profile I); 26.6% of the patients had total and IgM antibodies at IFI without CF antibodies (profile II); 31.6% of the patients had only total antibodies at IFI without specific IgM and without CF antibodies (profile III); 11.3% of the patients were Chlamydia antibody negative (profile IV). In the control group of 50 pregnant women apparently non infected, the profile distribution was 2% profile I, 8% profile II, 38% profile III, and 54% profile IV. Detection of IgM antibodies to Chlamydia trachomatis in 57% of patients with salpingitis, taking only one specimen, suggested recent or active chlamydial infection. CF antibodies indicated diffuse infection. Total antibodies correlated well with IgG antibodies detected by ELISA. Their finding was by no means diagnosis for Chlamydia being the cause of tubal infection, although titers observed in salpingitis patients were higher than in controls.

[Lymphocyte subpopulations in hemophilic patients]. / Etude des sous-populations lymphocytaires chez l'hémophile.

Monoclonal antibody analysis of peripheral blood T-cell subsets was performed in 23 multitransfused haemophiliacs, 5 children and 10 adults. Although none of the patients exhibited symptoms of acquired immune deficiency, 5 of them showed an abnormally low proportion of T-cells with reversal of the OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) ratio. No evidence of cytomegalovirus infection was found. A search for antibodies to human leukaemia virus antigen P24 gave negative results. The relationship between this abnormality and transfusions is discussed.

[Non-gonococcal urethritis and cervicitis. Isolation of Chlamydia trachomatis and detection of anti-Chlamydia antibodies by indirect immunofluorescence]. / Urétrites et cervicites non gonococciques. Isolement de Chlamydia trachomatis et détection des anticorps anti-chlamydiens par immunofluorescence indirecte.

The responsibility of Chlamydia trachomatis in non-gonococcal urethritis and cervicitis was investigated in 267 patients of both sexes. It was confirmed in 36.3% of patients with urethritis and 20.9% of patients with cervicitis by isolating C. trachomatis on Hela 229 cells in the presence of cytochalasin B. No clinical feature specific of C. trachomatis infection could be elicited. The patients were tested for total IgM-type serum anti-chlamydia antibodies by indirect immunofluorescence (IF), using as antigen the inclusions formed in Hela 229 cells by an L2 serotype of C. trachomatis. The serological study was also performed in 86 blood-donors used as controls. The diagnostic value of IF serology is limited in lower genito-urinary infections; the presence of specific IgM's correlates well with the isolation of C. trachomatis, but these IgM's are not detected in protracted urethritis or cervicitis. In such cases, the aetiological diagnosis can only be made by isolation of C. trachomatis from the focus of infection.

[Prevalence of HIV-1, HIV-2 and HTLV-1 infections. Experience in a Parisian center for sexually transmitted diseases]. / Prévalence des infections par les VIH 1, VIH 2 et HTLV 1. Expérience d'un centre des maladies sexuellement transmissibles à Paris.

Human immunodeficiency virus (HIV) infection is, to a great extent, a sexually transmitted disease (STD). Its diffusion among the heterosexual population is still limited. STD treatment centres are particularly well organized to watch this diffusion. At the STD centre of the Saint-Louis hospital, Paris, we conducted a 6-week prospective study concerning the systematic detection of HIV-1 infection in 240 consecutive female out-patients in 1988, and in 504 male out-patients in 1989. The results obtained were as follow: 5/240 women (2.1 percent) and 19/504 men (3.8 percent) were seropositive for HIV-1. Out of these 24 subjects, 15 did not know they were seropositive. Predictive factors for seropositivity were male homosexuality, addiction to heroin and, in women, drug addicts as sex partners. Altogether, 23 of the 24 seropositive subjects had the classical risk factors for HIV-1 infection. None of the 744 subjects in this study were HIV-2 seropositive, and only 1 out of 504 men was HTLV-1 seropositive. We conclude that the prevalence of HIV-1 infection was high in our centre, and this prompts us to suggest that the serological test should be proposed to all out-patients and that patient's education and preventive measures should be organized by STD centres, even though the infection is still limited to patients at a particularly high risk (drug addicts, homosexuals, country of origin).

[Cutaneous manifestations of cytomegalovirus infections]. / Manifestations cutanées des infections à cytomégalovirus.

The cutaneous manifestations that occur commonly in cytomegalovirus (CMV) infections are erythematous maculopapular eruptions or purpuric rashes . But, CMV has been detected in chronic mucosal and skin ulcerations, benign tumour-like lesions and eroded gingivitis. Most of these cutaneous lesions are secondary to vasculitis of the small dermal, subcutaneous tissue or submucosa vessels. The authors discuss the different physiopathological mechanisms which may be involved in the development of these viral-induced vasculitis. Dermal erythropoiesis in neonatal infants and localized granulomatous lesions have been also reported.