Virological markers in the cerebrospinal fluid from HIV-1-infected individuals.

We analysed 127 specimens of cerebrospinal fluid (CSF) from 118 HIV-1-infected individuals at different stages of infection. Intrathecal antibody synthesis was evident in 23 samples tested and was more frequently directed against HIV than against rubella virus, herpes simplex virus, varicella zoster virus or cytomegalovirus. HIV was isolated from only 14% of the 127 CSF specimens, but from 82% of CSF-paired blood samples. HIV antigen was detected in 12% of CSF specimens and 44% of paired plasma samples. Twenty specimens analysed using the polymerase chain reaction (PCR) detected proviral DNA in 75% of CSF specimens. The low rate of virus recovery from CSF was caused by neither the freezing of specimens prior to culture nor therapy. In contrast, virus isolation from CSF was significantly associated with CSF cell count. Virus isolation and antigen detection in CSF were not correlated with either the Centers for Disease Control disease stage or the peripheral CD4+ lymphocyte count, whereas viraemia was significantly associated with a low CD4+ lymphocyte count. Moreover, virus isolation and antigen detection in CSF were not associated with symptoms of subacute HIV encephalitis, suggesting that these markers are not of potential value in the diagnosis of HIV-specific neurologic complications. The value of PCR in this field merits further investigation.

Respective roles of immune and nutritional factors in the priming of the immune response in the elderly.

Ninety-six institutionalized elderly (greater than 70 years old) (mean age: 82 +/- 7 years) subjects, negative for tetanus toxoid antibodies were primed with tetanus toxoid vaccination and dinitrochlorobenzene (DNCB). Correlations were studied between some immunological parameters, nutritional parameters prior to immunization and the immune response intensity after it. Levels of tetanus toxoid specific IgG (ELISA assay) were positively correlated with monocyte phagocytosis, DNCB response and prealbumin levels, and negatively correlated with total IgG, monocyte immune degradation and tetanus toxoid lymphocyte stimulation. No correlation was observed with IgA, IgM, PHA stimulation. Tetanus toxoid lymphocyte stimulation correlated positively with response to DNCB, and negatively with tetanus toxoid IgG as well as total IgG. DNCB response correlated with prealbumin, tetanus toxoid IgG and tetanus toxoid lymphocyte stimulation. Therefore, it appears that malnutrition, as measured by prealbumin level, is one of the main factors contributing to the inconstant senile immunodeficiency. Monocyte antigenic degradation function unaltered with age can impair immune response while conserved or increased phagocytosis enhances immune response in the elderly. High total IgG levels were linked with low specific responses to priming antigens. High specific antibody levels also correlated negatively with cellular specific response. It is assumed that regulatory IgG antibody accumulation, likely anti-idiotypic antibodies, play an important role in senile immunological depletion.

Absence of humoral autoimmunity in peripartum cardiomyopathy. A comparative study in Niger.

The authors report a humoral immunity study in 39 black Nigerian women with peripartum cardiomyopathy. Serum immunoglobulins (IgG, IgA, IgM) assay, evaluation of serum immune complexes (immunonephelemetric method) and of heart muscle autoantibodies (indirect immunofluorescent double layer technique in heart muscle of the rat) were made. Forty breastfeeding black Nigerian women without cardiac disease were the controls. Differences between serum immunoglobulins, circulating immune complexes and heart muscle autoantibodies are not significant. This study demonstrates the absence of a humoral autoimmunity process in peripartum cardiomyopathy.

[Juvenile multiple myeloma. A Nigerian case]. / Myélome multiple juvénile. Un cas nigérien.

One case of juvenile multiple myeloma of the IgG-kappa type, with lytic lesions of the skull, is reported in a 14-year old Nigerian Fulani girl. The outcome was rapidly fatal. This disease is extremely rare: only 2 other documented cases (2 girls aged 13 and 12) have been found in the literature, under the age of 15.

[Anonymous and free-of-charge detection of human immunodeficiency virus infection. 20-months' experience at a center]. / Dépistage anonyme et gratuit de l'infection par le virus de l'immunodéficience humaine. Expérience d'un centre pendant 20 mois.

The results of 20 months' activity of the anonymous and free-of-charge detection centre of the Pitié-Salpêtrière hospital group, Paris, concerning human immunodeficiency virus infection (HIV) are presented. During that period, 3,480 persons consulted and 3,332 anonymous questionnaires were filled and returned: 20.5 percent of the subjects were homosexuals, 6.5 percent were drug-addicts and 73 percent were non drug-addict heterosexuals; 31 percent used condoms. A total of 3,398 blood samples were collected; 232 sera were positive or undetermined for HIV-1 and/or HIV-2 by the ELISA method; 132 Western Blot tests confirmed the positivity for HIV-1 but not for HIV-2. The overall serum positivity was 4 percent; 18.3 percent of drug-addicts, 9.5 percent of homosexuals and 0.9 percent of heterosexuals were HIV positive. Among seropositive subjects, 51 percent were homosexuals, 27 percent were drug-addicts, 4 percent were homosexual drug-addicts and 18 percent were heterosexuals (43 percent of these had had multiple partners); condoms were used by 59 percent of HIV positive subjects. The percentage of HIV positive subjects in our series was lower than that estimated in populations at risk (drug-addicts 50 percent, homosexuals 32 percent); it was similar to the percentages found in other detection centres (5 to 6 percent). Most seropositive patients belong to the category of persons who are the first to be struck by HIV. The heterosexual population is relatively spared, but most of the recent seroconversions have occurred in this group.

[Prospects and current data in antiviral chemotherapy]. / Perspectives et données présentes en chimiothérapie antivirale.

The advances achieved in our knowledge on the virus multiplication cycle and the challenge created by the advent of AIDS have resulted in a rational development of new antiviral agents. However, antiviral chemotherapy is hindered by several obstacles: (1) most antiviral drugs are cytotoxic, with the exception of acyclovir which owes its remarkable safety to its activation by the thymidine kinase of the herpes simplex viruses and of the varicella-zoster virus; (2) the risk of selecting resistant strains by mutation of viral enzymes is the unavoidable price to pay for the specificity of new antiviral agents which interfere with these enzymes; so far, this risk seems to apply only to immunocompromised patients; (3) latent viral infection, defined as the lack of active multiplication of the virus, cannot be eradicated by the antiviral drugs available at present since these drugs are inhibitors of viral multiplication. However, anti-sens oligonucleotides could, at least in theory, be used to treat this type of infection which is not limited to the Retroviridae or Herpesviridae families. Finally, antiviral drugs active against life-threatening infections that are as common as rabies and the severe forms of measles or viral hepatitis remain to be discovered.

Prevalence of serum antibodies to herpes simplex virus types 1 and 2: application of an ELISA technique to 100 cases of anogenital herpes.

Sera of 100 patients affected by anogenital herpes were tested by an enzyme-linked immunosorbent assay (ELISA) technique using partially purified antigens obtained by extraction from the nuclei of infected Vero cells. Herpes simplex virus type 1 (HSV-1) was isolated from the anogenital lesions of 17 patients and herpes simplex virus type 2 (HSV-2) from 83 patients. The relative proportions of antibody of the IgG class to HSV-1 and HSV-2 were determined and their ratio (R) was calculated, except for 23 patients for whom the corrected optical density (COD) obtained for HSV-1 or HSV-2 antibody was less than the lower value limit of 0.025. A predominance of HSV-2 antibody (R less than 1) was found in 40 patients and was uniformly associated with isolation of HSV-2, whereas a predominance of HSV-1 antibody (R greater than 1) in 37 patients was found in the presence of infection with HSV-1 in 11 (30%) and with HSV-2 in 26 (70%) patients. This study also confirms the association of a higher frequency of recurrences with HSV-2: among the 55 patients with recurrent herpes, those from whom HSV-2 was isolated had a history of more recurrences than those infected with HSV-1 (P less than 0.05; Mann and Whitney's nonparametric test). No correlation between the number of recurrences and the level of HSV-2 antibody was found.

[Specific IgM of cytomegaloviruses and primary infection in kidney transplant patients]. / IgM spécifiques du cytomégalovirus et primo-infection chez les transplantés rénaux.

In 20 renal transplant recipients suffering from symptomatic CMV infection we looked if a specific IgM response was indicative of a primary infection. By an ELISA technique we investigated the specific IgG and IgM in a pair of sera taken at the time of the transplantation and later at the time of the CMV isolation. For 7 out of 8 patients exhibiting an IgM response in the late serum, the pretransplant serum did not contain either IgG or IgM specific antibodies. Therefore the specific IgM response was associated in 7 out of 8 patients with a primary CMV infection. Nevertheless in 6 other primary infected patients no specific IgM response was detected. Otherwise rheumatoid factors appeared in each primary infected patient developing a specific IgG response, with or without specific IgM response.

Intrathecal synthesis of proteins: from immunoglobulins to prealbumin.

The assessment of proteins intrathecal synthesis (ITS) is an essential step in the CSF analysis. It can be established qualitatively by different ratios and quantitatively by empirical formulae. Schuller and Sagar's formula was proposed 10 years ago for the calculation of IgG ITS. From this calculation, the antibody specific activity of intrathecal immunoglobulins may be also evaluated. The same principle may be used for complement components and for different other CSF proteins. Two examples (concerning Fibronectin and prealbumin ITS) demonstrate the usefulness of this approach, which can be programmed by a computer.

Comparison of an amplified enzyme-linked immunosorbent assay with procedures based on molecular biology for assessing human immunodeficiency virus type 1 viral load.

The sensitivity of the enzyme-linked amplified sorbent test (ELAST) was compared with those of other classic enzyme-linked immunosorbent assays (ELISAs), with or without previous acidic immunocomplex dissociation (ICD), in a series of samples at different stages of human immunodeficiency virus type 1 (HIV-1) infection. The limit of viral detection of ELAST was assessed with fresh HIV-1 preparations quantified by reverse transcription-PCR and with the P24 antigen (Ag) Sanofi Pasteur Calibrator containing lyophilized virus. The P24 Ag detection capacity of ELAST was compared with that of NASBA in samples obtained from infected subjects with less than 250 CD4+ cells. The results of the present study show that ELAST was the most sensitive method for detecting P24 Ag compared to classic ELISA and ICD plus ELISA. ELAST was able to detect 0.5 pg of P24 Ag per ml in a whole virus preparation and the equivalent of 330 to 1,000 RNA copies/ml of HIV. The rate of detection of P24 Ag was always higher in subjects with low levels of anti-P24 antibodies. The number of positive results was dramatically enhanced (from 37% to 94% for subjects with <250 CD4+ cells) when the incubation period was prolonged from 1 to 16 h. In a third series of 84 samples (<250 CD4+ cells) tested in parallel, NASBA yielded 83% of the positive results and ELAST yielded 79%. Considering the high sensitivity, low cost, simplicity of equipment (only a plate reader), and possibility for full automation, ELAST appears to be a promising new tool for measuring viral load, especially in areas with few resources, in which the procedures based on molecular biology techniques may be difficult to install.

[Plasma zinc levels in elderly hospitalized subjects. Correlation with other nutritional and immunological markers and survival]. / Le zinc plasmatique chez le sujet âgé institutionnalisé. Corrélations avec d'autres marqueurs nutritionnels, immunologiques et la survie.

Plasma zinc levels were measured in 95 elderly patients hospitalized in a long stay unit and in 100 healthy controls under 65 years of age. Plasma zinc concentrations were significantly lower in the elderly patients, as compared to the younger subjects (p 0.001). The correlations with serum prealbumin (p 0.05) and serum albumin (p 0.05) concentrations and the frequent association with protein-calorie malnutrition suggest that the low serum zinc levels mirror a low dietary zinc intake. Immunological tests in the elderly show moderate lymphopenia, high serum IgA and frequent depression of delayed cutaneous hypersensitivity to DNCB and PHA. We find a significant correlation between plasma zinc concentration and peripheral blood lymphocyte counts, but not the other immunological parameters. Linear discriminant analysis shows that the association of low plasma zinc values, low serum protein concentration and high serum IgG concentration implies poor prognosis.

Detection of antibodies to human herpesvirus-6 using immunofluorescence assay.

A serological study of human herpesvirus-6 (HHV-6) infection was performed by means of immunofluorescence assay on fixed HHV-6-infected cells. Comparison between indirect immunofluorescence assay (IFA) and anticomplement immunofluorescence assay (ACIF) showed that the latter test was the most appropriate for HHV-6 serology, although both methods exhibited identical sensitivity. ACIF, which was performed on HSB2 cells infected with the HBLV strain (provided by S.Z. Salahuddin), was then used to determine the titre of HHV-6 antibodies in serum by end-point dilution. The sera from 115 healthy subjects and 99 patients with presumed viral infection were tested. A similar distribution of HHV-6 titres was evidenced in both cases and the rate of individuals exhibiting a positive titre of 20 and above was about 30% of the whole population studied. No serological cross-reactivity was observed between HHV-6 and other herpesviruses, suggesting that the HHV-6 ACIF test was quite specific.